Macrophage RAGE activation is proinflammatory in NASH.

Intrahepatic macrophages in nonalcoholic steatohepatitis (NASH) are heterogenous and include proinflammatory recruited monocyte-derived macrophages. The receptor for advanced glycation endproducts (RAGE) is expressed on macrophages and can be activated by damage associated molecular patterns (DAMPs) upregulated in NASH, yet the role of macrophage-specific RAGE signaling in NASH is unclear. Therefore, we hypothesized that RAGE-expressing macrophages are proinflammatory and mediate liver inflammation in NASH. Compared with healthy controls, RAGE expression was increased in liver biopsies from patients with NASH. In a high-fat, -fructose, and -cholesterol-induced (FFC)-induced murine model of NASH, RAGE expression was increased, specifically on recruited macrophages. FFC mice that received a pharmacological inhibitor of RAGE (TTP488), and myeloid-specific RAGE KO mice (RAGE-MKO) had attenuated liver injury associated with a reduced accumulation of RAGE+ recruited macrophages. Transcriptomics analysis suggested that pathways of macrophage and T cell activation were upregulated by FFC diet, inhibited by TTP488 treatment, and reduced in RAGE-MKO mice. Correspondingly, the secretome of ligand-stimulated BM-derived macrophages from RAGE-MKO mice had an attenuated capacity to activate CD8+ T cells. Our data implicate RAGE as what we propose to be a novel and potentially targetable mediator of the proinflammatory signaling of recruited macrophages in NASH.

Stanford University School of Medicine: Our Neurosurgical Heritage.

The legacy of Stanford University's Department of Neurosurgery began in 1858, with the establishment of a new medical school on the West Coast. Stanford Neurosurgery instilled an atmosphere of dedication to neurosurgical care, scientific research, education, and innovation. We highlight key historical events leading to the formation of the medical school and neurosurgical department, the individuals who shaped the department's vision and expansion, as well as pioneering advances in research and clinical care. The residency program was started in 1961, establishing the basis of the current education model with a strong emphasis on training future leaders, and the Moyamoya Center, founded in 1991, became the largest Moyamoya referral center in the United States. The opening of Stanford Stroke Center (1992) and seminal clinical trials resulted in a significant impact on cerebrovascular disease by expanding the treatment window of IV thrombolysis and intra-arterial thrombectomy. The invention and implementation of CyberKnife® (1994) marks another important event that revolutionized the field of radiosurgery, and the development of Stanford's innovative Brain Computer Interface program is pushing the boundaries of this specialty. The more recent launch of the Neurosurgery Virtual Reality and Simulation Center (2017) exemplifies how Stanford is continuing to evolve in this ever-changing field. The department also became a model for diversity within the school as well as nationwide. The growth of Stanford Neurosurgery from one of the youngest neurosurgery departments in the country to a prominent comprehensive neurosurgery center mirrors the history of neurosurgery itself: young, innovative, and willing to overcome challenges.

Matched-pair analysis of patients with ischemic stroke undergoing thrombectomy using next-generation balloon guide catheters.

BACKGROUND: Balloon guide catheters (BGCs) have not been widely adopted, possibly due to the incompatibility of past-generation BGCs with large-bore intermediate catheters. The next-generation BGC is compatible with large-bore catheters. We compared outcomes of thrombectomy cases using BGCs versus conventional guide catheters. METHODS: We conducted a retrospective study of 110 thrombectomy cases using BGCs (n=55) and non-BGCs (n=55). Sixty consecutive thrombectomy cases in whom the BOBBY BGC was used at a single institution between February 2021 and March 2022 were identified. Of these, 55 BGC cases were 1:1 matched with non-BGC cases by proceduralists, age, gender, stent retriever + aspiration device versus aspiration-only, and site of occlusion. First-pass effect was defined as Thrombolysis In Cerebral Infarction 2b or higher with a single pass. RESULTS: The BGC and non-BGC cohorts had similar mean age (67.2 vs 68.9 years), gender distribution (43.6% vs 47.3% women), median initial National Institutes of Health Stroke Scale score (14 vs 15), and median pretreatment ischemic core volumes (12 mL vs 11.5 mL). BGC and non-BGC cases had similar rates of single pass (60.0% vs 54.6%), first-pass effect (58.2% vs 49.1%), and complications (1.8% vs 9.1%). In aspiration-only cases, the BGC cohort had a significantly higher rate of first-pass effect (100% vs 50.0%, p=0.01). BGC was associated with a higher likelihood of achieving a modified Rankin Scale score of 2 at discharge (OR 7.76, p=0.02). No additional procedural time was required for BGC cases (46.7 vs 48.2 min). CONCLUSION: BGCs may be safely adopted with comparable procedural efficacy, benefits to aspiration-only techniques, and earlier functional improvement compared with conventional guide catheters.

ZFP92, a KRAB domain zinc finger protein enriched in pancreatic islets, binds to B1/Alu SINE transposable elements and regulates retroelements and genes.

Repressive KRAB domain-containing zinc-finger proteins (KRAB-ZFPs) are abundant in mammalian genomes and contribute both to the silencing of transposable elements (TEs) and to the regulation of developmental stage- and cell type-specific gene expression. Here we describe studies of zinc finger protein 92 (Zfp92), an X-linked KRAB-ZFP that is highly expressed in pancreatic islets of adult mice, by analyzing global Zfp92 knockout (KO) mice. Physiological, transcriptomic and genome-wide chromatin binding studies indicate that the principal function of ZFP92 in mice is to bind to and suppress the activity of B1/Alu type of SINE elements and modulate the activity of surrounding genomic entities. Deletion of Zfp92 leads to changes in expression of select LINE and LTR retroelements and genes located in the vicinity of ZFP92-bound chromatin. The absence of Zfp92 leads to altered expression of specific genes in islets, adipose and muscle that result in modest sex-specific alterations in blood glucose homeostasis, body mass and fat accumulation. In islets, Zfp92 influences blood glucose concentration in postnatal mice via transcriptional effects on Mafb, whereas in adipose and muscle, it regulates Acacb, a rate-limiting enzyme in fatty acid metabolism. In the absence of Zfp92, a novel TE-Capn11 fusion transcript is overexpressed in islets and several other tissues due to de-repression of an IAPez TE adjacent to ZFP92-bound SINE elements in intron 3 of the Capn11 gene. Together, these studies show that ZFP92 functions both to repress specific TEs and to regulate the transcription of specific genes in discrete tissues.

Intracranial Artery Morphology in Pediatric Moya Moya Disease and Moya Moya Syndrome.

BACKGROUND: Moya Moya disease (MMD) and Moya Moya syndrome (MMS) are cerebrovascular disorders, which affect the internal carotid arteries (ICAs). Diagnosis and surveillance of MMD/MMS in children mostly rely on qualitative evaluation of vascular imaging, especially MR angiography (MRA). OBJECTIVE: To quantitatively characterize arterial differences in pediatric patients with MMD/MMS compared with normal controls. METHODS: MRA data sets from 17 presurgery MMD/MMS (10M/7F, mean age = 10.0 years) patients were retrospectively collected and compared with MRA data sets of 98 children with normal vessel morphology (49 male patients; mean age = 10.6 years). Using a level set segmentation method with anisotropic energy weights, the cerebral arteries were automatically extracted and used to compute the radius of the ICA, middle cerebral artery (MCA), anterior cerebral artery (ACA), posterior cerebral artery (PCA), and basilar artery (BA). Moreover, the density and the average radius of all arteries in the MCA, ACA, and PCA flow territories were quantified. RESULTS: Statistical analysis revealed significant differences comparing children with MMD/MMS and those with normal vasculature ( P < .001), whereas post hoc analyses identified significantly smaller radii of the ICA, MCA-M1, MCA-M2, and ACA ( P < .001) in the MMD/MMS group. No significant differences were found for the radii of the PCA and BA or any artery density and average artery radius measurement in the flow territories ( P > .05). CONCLUSION: His study describes the results of an automatic approach for quantitative characterization of the cerebrovascular system in patients with MMD/MMS with promising preliminary results for quantitative surveillance in pediatric MMD/MMS management.

Phenotypic Heterogeneity among GBA p.R202X Carriers in Lewy Body Spectrum Disorders.

We describe the clinical and neuropathologic features of patients with Lewy body spectrum disorder (LBSD) carrying a nonsense variant, c.604C>T; p.R202X, in the glucocerebrosidase 1 (GBA) gene. While this GBA variant is causative for Gaucher's disease, the pathogenic role of this mutation in LBSD is unclear. Detailed neuropathologic evaluation was performed for one index case and a structured literature review of other GBA p.R202X carriers was conducted. Through the systematic literature search, we identified three additional reported subjects carrying the same GBA mutation, including one Parkinson's disease (PD) patient with early disease onset, one case with neuropathologically-verified LBSD, and one unaffected relative of a Gaucher's disease patient. Among the affected subjects carrying the GBA p.R202X, all males were diagnosed with Lewy body dementia, while the two females presented as PD. The clinical penetrance of GBA p.R202X in LBSD patients and families argues strongly for a pathogenic role for this variant, although presenting with a striking phenotypic heterogeneity of clinical and pathological features.

Age-dependent Intracranial Artery Morphology in Healthy Children.

PURPOSE: Evaluation of intracranial artery morphology plays an important role in diagnosing a variety of neurovascular diseases. In addition to clinical symptoms, diagnosis currently relies on qualitative rather than quantitative evaluation of vascular imaging sequences, such as magnetic resonance angiography (MRA). However, there is a paucity of literature on normal arterial morphology in the pediatric population across brain development. We aimed to quantitatively assess normal, age-related changes in artery morphology in children. METHODS: We performed retrospective analysis of pediatric MRA data obtained from a tertiary referral center. An MRA dataset from 98 children (49 boys/49 girls) aged 0.6-20 years (median = 11.5 years) with normal intracranial vasculature was retrospectively collected between 2011 and 2018. All arteries were automatically segmented to determine the vessel radius. Using an atlas-based approach, the average radius and density of arteries were measured in the three main cerebral vascular territories and the radius of five major arteries was determined at corresponding locations. RESULTS: The radii of the major arteries as well as the average artery radius and density in the different vascular territories in the brain remained constant throughout childhood and adolescence (|r| < 0.369 in all cases). CONCLUSION: This study presents the first automated evaluation of intracranial vessel morphology on MRA across childhood. Our results can serve as a framework for quantitative evaluation of cerebral vessel morphology in the setting of pediatric neurovascular diseases.

Incorporating patient-centered quality-of-life measures for outcome assessment after Chiari malformation type I decompression in a pediatric population: a pilot study.

OBJECTIVE: Optimal management of pediatric Chiari malformation type I (CM-I) is much debated, chiefly due to the lack of validated tools for outcome assessment, with very few tools incorporating patient-centered measures of health-related quality of life (HRQOL). Although posterior fossa decompression (PFD) benefits a subset of patients, prediction of its impact across patients is challenging. The primary aim of this study was to investigate the role of patient-centered HRQOL measures in the assessment and prediction of outcomes after PFD. METHODS: The authors collected HRQOL data from a cohort of 20 pediatric CM-I patients before and after PFD. The surveys included assessments of selected Patient-Reported Outcomes Measurement Information System (PROMIS) health domains and were used to generate the PROMIS preference (PROPr) score, which is a measure of HRQOL. PROMIS is a reliable standardized measure of HRQOL domains such as pain, fatigue, depression, and physical function, which are all relevant to CM-I. The authors then compared the PROPr scores with Chicago Chiari Outcome Scale (CCOS) scores derived from time-matched clinical documentation. Finally, the authors used the PROPr scores as an outcome measure to predict postsurgical HRQOL improvement at 1 year on the basis of patient demographic characteristics, comorbidities, and radiological and physical findings. The Wilcoxon signed-rank test, Mann-Whitney U-test, and Kendall's correlation were used for statistical analysis. RESULTS: Aggregate analysis revealed improvement of pain severity after PFD (p = 0.007) in anatomical patterns characteristic of CM-I. Most PROMIS domain scores trended toward improvement after surgery, with anxiety and pain interference reaching statistical significance (p < 0.002 and p < 0.03, respectively). PROPr scores also significantly improved after PFD (p < 0.008). Of the baseline patient characteristics, preexisting scoliosis was the most accurate negative predictor of HRQOL improvement after PFD (median -0.095 vs 0.106, p < 0.001). A correlation with modest magnitude (Kendall's tau range 0.19-0.47) was detected between the patient-centered measures and CCOS score. CONCLUSIONS: The authors observed moderate improvement of HRQOL, when measured using a modified panel of PROMIS question banks, in this pilot cohort of pediatric CM-I patients after PFD. Further investigations are necessary to validate this tool for children with CM-I and to determine whether these scores correlate with clinical and radiographic findings.

Defining and describing treatment heterogeneity in new-onset idiopathic lower back and extremity pain through reconstruction of longitudinal care sequences.

BACKGROUND CONTEXT: Despite established guidelines, long-term management of surgically-treated low back pain (LBP) and lower extremity pain (LEP) remains heterogeneous. Understanding care heterogeneity could inform future approaches for standardization of practices. PURPOSE: To describe treatment heterogeneity in surgically-managed LBP and LEP. STUDY DESIGN/SETTING: Retrospective study of a nationwide commercial database spanning inpatient and outpatient encounters for enrollees of eligible employer-supplied healthcare plans (2007-2016). PATIENT SAMPLE: A population-based sample of opioid-naïve adult patients with newly-diagnosed LBP or LEP were identified. Inclusion required at least 12-months of pre-diagnosis and post-diagnosis continuous follow-up. EXPOSURE: Included treatments/evaluations include conservative management (chiropractic manipulative therapy, physical therapy, epidural steroid injections), imaging (x-ray, MRI, CT), pharmaceuticals (opioids, benzodiazepines), and spine surgery (decompression, fusion). OUTCOME MEASURES: Primary outcomes-of-interest were 12-month net healthcare expenditures (inpatient and outpatient) and 12-month opioid usage. METHODS: Analyses include interrogation of care sequence heterogeneity and temporal trends in sequence-initiating services. Comparisons were conducted in the framework of sequence-specific treatment sequences, which reflect the personalized order of healthcare services pursued by each patient. Outlier sequences characterized by high opioid use and costs were identified from frequently observed surgical treatment sequences using Mahalanobis distance. RESULTS: A total of 2,496,908 opioid-naïve adult patients with newly-diagnosed LBP or LEP were included (29,519 surgical). In the matched setting, increased care sequence heterogeneity was observed in surgical patients (0.51 vs. 0.12 previously-unused interventions/studies pursued per month). Early opioid and MRI use has decreased between 2008 and 2015 but is matched by increases in early benzodiazepine and x-ray use. Outlier sequences, characterized by increased opioid use and costs, were found in 5.8% of surgical patients. Use of imaging prior to conservative management was common in patients pursuing outlier sequences compared to non-outlier sequences (96.5% vs. 63.8%, p<.001). Non-outlier sequences were more frequently characterized by early conservative interventions (31.9% vs. 7.4%, p<.001). CONCLUSIONS: Surgically-managed LBP and LEP care sequences demonstrate high heterogeneity despite established practice guidelines. Outlier sequences associated with high opioid usage and costs can be identified and are characterized by increased early imaging and decreased early conservative management. Elements that may portend suboptimal longitudinal management could provide opportunities for standardization of patient care.

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.

Artificial intelligence for automatic cerebral ventricle segmentation and volume calculation: a clinical tool for the evaluation of pediatric hydrocephalus.

OBJECTIVE: Imaging evaluation of the cerebral ventricles is important for clinical decision-making in pediatric hydrocephalus. Although quantitative measurements of ventricular size, over time, can facilitate objective comparison, automated tools for calculating ventricular volume are not structured for clinical use. The authors aimed to develop a fully automated deep learning (DL) model for pediatric cerebral ventricle segmentation and volume calculation for widespread clinical implementation across multiple hospitals. METHODS: The study cohort consisted of 200 children with obstructive hydrocephalus from four pediatric hospitals, along with 199 controls. Manual ventricle segmentation and volume calculation values served as "ground truth" data. An encoder-decoder convolutional neural network architecture, in which T2-weighted MR images were used as input, automatically delineated the ventricles and output volumetric measurements. On a held-out test set, segmentation accuracy was assessed using the Dice similarity coefficient (0 to 1) and volume calculation was assessed using linear regression. Model generalizability was evaluated on an external MRI data set from a fifth hospital. The DL model performance was compared against FreeSurfer research segmentation software. RESULTS: Model segmentation performed with an overall Dice score of 0.901 (0.946 in hydrocephalus, 0.856 in controls). The model generalized to external MR images from a fifth pediatric hospital with a Dice score of 0.926. The model was more accurate than FreeSurfer, with faster operating times (1.48 seconds per scan). CONCLUSIONS: The authors present a DL model for automatic ventricle segmentation and volume calculation that is more accurate and rapid than currently available methods. With near-immediate volumetric output and reliable performance across institutional scanner types, this model can be adapted to the real-time clinical evaluation of hydrocephalus and improve clinician workflow.

Outcomes After Cervical Disc Arthroplasty Versus Stand-Alone Anterior Cervical Discectomy and Fusion: A Meta-Analysis.

STUDY DESIGN: Systemic review and meta-analysis. OBJECTIVES: To review and compare surgical outcomes for patients undergoing stand-alone anterior cervical discectomy and fusion (ACDF) versus cervical disc arthroplasty (CDA) for the treatment of cervical spine disease. METHODS: A systematic search was performed on PubMed, Medline, and the Cochrane Library. Comparative trials measuring outcomes of patients undergoing CDA and stand-alone ACDF for degenerative spine disease in the last 10 years were selected for inclusion. After data extraction and quality assessment, statistical analysis was performed with R software metafor package. The random-effects model was used if there was heterogeneity between studies; otherwise, the fixed-effects model was used. RESULTS: In total, 12 studies including 859 patients were selected for inclusion in the meta-analysis. Patients undergoing stand-alone ACDF had a statistically significant increase in postoperative segmental angles (mean difference 0.85° [95% confidence interval = 0.35° to 1.35°], P = .0008). Patients undergoing CDA had a decreased rate of developing adjacent segmental degeneration (risk ratio = 0.56 [95% confidence interval = -0.06 to 1.18], P = .0745). Neck Disability Index, Japanese Orthopedic Association score, Visual Analogue Scale of the arm and neck, as well as postoperative cervical angles were similar between the 2 treatments. CONCLUSIONS: When compared with CDA, stand-alone ACDF offers similar clinical outcomes for patients and leads to increased postoperative segmental angles. We encourage further blinded randomized trials to compare rates of adjacent segmental degeneration and other postoperative outcomes between these 2 treatments options.

Mortality prediction and long-term outcomes for civilian cerebral gunshot wounds: A decision-tree algorithm based on a single trauma center.

Gunshot wounds (GSW) are one of the most lethal forms of head trauma. The lack of clear guidelines for civilian GSW complicates surgical management. We aimed to develop a decision-tree algorithm for mortality prediction and report long-term outcomes on survivors based on 15-year data from our level 1 trauma center. We retrospectively reviewed 96 consecutive patients who presented with cerebral GSWs between 2003 and 2018. Clinical information from our trauma database, EMR, and relevant imaging scans was reviewed. A decision-tree model was constructed based on variables showing significant differences between survivors and non-survivors. After excluding patients who died at arrival, 54 patients with radiologically confirmed intracranial injury were included. Compared to survivors (51.9%), non-survivors (48.1%) were significantly more likely to have perforating (entry and exit wound), as opposed to penetrating (entry wound only), injuries. Bi-hemispheric and posterior fossa involvement, cerebral herniation, and intraventricular hemorrhage were more commonly present in non-survivors. Based on the decision-tree, Glasgow Coma Scale (GCS) > 8 and penetrating, uni-hemispheric injury predicted survival. Among patients with GCS ≤ 8 and normal pupillary response, lack of 1) posterior fossa involvement, 2) cerebral herniation, 3) bi-hemispheric injury, and 4) intraventricular hemorrhage, were associated with survival. Favorable long-term outcomes (mean follow-up 34.4 months) were possible for survivors who required neurosurgery and stable patients who were conservatively managed. We applied clinical and radiological characteristics that predicted survival to construct a decision-tree to facilitate surgical decision-making for GSW. Further validation of the algorithm in a large patient setting is recommended.

Utilization of Novel High-Resolution, MRI-Based Vascular Imaging Modality for Preoperative Stereoelectroencephalography Planning in Children: A Technical Note.

INTRODUCTION: Stereoelectroencephalography (SEEG) is a powerful intracranial diagnostic tool that requires accurate imaging for proper electrode trajectory planning to ensure efficacy and maximize patient safety. Computed tomography (CT) angiography and digital subtraction angiography are commonly used, but recent developments in magnetic resonance angiography allow for high-resolution vascular visualization without added risks of radiation. We report on the accuracy of electrode placement under robotic assistance planning utilizing a novel high-resolution magnetic resonance imaging (MRI)-based imaging modality. METHODS: Sixteen pediatric patients between February 2014 and October 2017 underwent SEEG exploration for epileptogenic zone localization. A gadolinium-enhanced 3D T1-weighted spoiled gradient recalled echo sequence with minimum echo time and repetition time was applied for background parenchymal suppression and vascular enhancement. Electrode placement accuracy was determined by analyzing postoperative CT scans laid over preoperative virtual electrode trajectory paths. Entry point, target point, and closest vessel intersection were measured. RESULTS: For any intersection along the trajectory path, 57 intersected vessels were measured. The mean diameter of an intersected vessel was 1.0343 ± 0.1721 mm, and 21.05% of intersections involved superficial vessels. There were 157 overall intersection + near-miss events. The mean diameter for an involved vessel was 1.0236 ± 0.0928 mm, and superficial vessels were involved in 20.13%. Looking only at final electrode target, 3 intersection events were observed. The mean diameter of an intersected vessel was 1.0125 ± 0.2227 mm. For intersection + near-miss events, 24 were measured. An involved vessel's mean diameter was 1.1028 ± 0.2634 mm. For non-entry point intersections, 45 intersected vessels were measured. The mean diameter for intersected vessels was 0.9526 ± 0.0689 mm. For non-entry point intersections + near misses, 126 events were observed. The mean diameter for involved vessels was 0.9826 ± 0.1008 mm. CONCLUSION: We believe this novel sequence allows better identification of superficial and deeper subcortical vessels compared to conventional T1-weighted gadolinium-enhanced MRI.

Predictors of Cervical Vertebral and Carotid Artery Dissection During Blunt Trauma: Experience From a Level 1 Trauma Center.

BACKGROUND: The current data available to identify the factors associated with vertebral and carotid artery dissection in the trauma setting are conflicting, and further research is needed to accurately assess these predictors. METHODS: The data from 950 patients who had undergone neck computed tomography angiography (CTA) at a level 1 trauma center were analyzed. Of the 950 patients, 435 were included who had undergone neck CTA for blunt traumatic injuries. The mechanism of injury was classified as high or low impact according to the hospital criteria for trauma. Positive neurological signs included altered mental status (Glasgow coma scale score ≤15 than baseline) or focal neurological deficits. Fractures and dissections were radiologically confirmed. Multivariable logistic regression software was used to analyze the data. RESULTS: Of the 435 patients, 236 (54.25%) had experienced high-impact injuries, 124 (28.51%) had vertebral fractures (including 63 displaced fractures [50.81%]), and 180 (41.38%) had had positive neurological signs on presentation. Of the 435 patients, cervical carotid artery injury had been diagnosed in 9 (2.07%), and 18 patients (4.14%) had had a cervical vertebral artery injury (VAI). Carotid artery injuries did not have significant associations with positive neurological signs, age, sex, mechanism of injury, or vertebral fracture (P > 0.05 for all). Positive neurological signs and vertebral fractures were significant predictors for VAI (odds ratio, 3.19; P < 0.05; odds ratio, 9.81; P < 0.001, respectively). Age, sex, mechanism of injury, and displacement of the vertebral fracture were not significant predictors for VAI (P > 0.05 for all). CONCLUSIONS: Positive neurological signs and the presence of cervical vertebral fractures are significant predictors for VAI. All trauma patients with cervical spine fractures and/or positive neurological findings should be considered for surveillance imaging with neck CTA and/or magnetic resonance angiography for vascular injury screening.

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.

Early Diffusion Magnetic Resonance Imaging Changes in Normal-Appearing Brain in Pediatric Moyamoya Disease.

BACKGROUND: Moyamoya disease often leads to ischemic strokes visible on diffusion-weighted imaging (DWI) and T2-weighted magnetic resonance imaging (MRI) with subsequent cognitive impairment. In adults with moyamoya, apparent diffusion coefficient (ADC) is correlated with regions of steal phenomenon and executive dysfunction prior to white matter changes. OBJECTIVE: To investigate quantitative global diffusion changes in pediatric moyamoya patients prior to explicit structural ischemic damage. METHODS: We retrospectively reviewed children (<20 yr old) with moyamoya disease and syndrome who underwent bypass surgery at our institution. We identified 29 children with normal structural preoperative MRI and without findings of cortical infarction or chronic white matter ischemic changes. DWI datasets were used to calculate ADC maps for each subject as well as for 60 age-matched healthy controls. Using an atlas-based approach, the cerebral white matter, cerebral cortex, thalamus, caudate, putamen, pallidum, hippocampus, amygdala, nucleus accumbens, and brainstem were segmented in each DWI dataset and used to calculate regional volumes and ADC values. RESULTS: Multivariate analysis of covariance using the regional ADC and volume values as dependent variables and age and gender as covariates revealed a significant difference between the groups (P < .001). Post hoc analysis demonstrated significantly elevated ADC values for children with moyamoya in the cerebral cortex, white matter, caudate, putamen, and nucleus accumbens. No significant volume differences were found. CONCLUSION: Prior to having bypass surgery, and in the absence of imaging evidence of ischemic stroke, children with moyamoya exhibit cerebral diffusion changes. These findings could reflect microstructural changes stemming from exhaustion of cerebrovascular reserve.

Altered cerebral perfusion in children with Langerhans cell histiocytosis after chemotherapy.

BACKGROUND AND PURPOSE: Children with Langerhans cell histiocytosis (LCH) may develop a wide array of neurological symptoms, but associated cerebral physiologic changes are poorly understood. We examined cerebral hemodynamic properties of pediatric LCH using arterial spin-labeling (ASL) perfusion magnetic resonance imaging (MRI). MATERIALS AND METHODS: A retrospective study was performed in 23 children with biopsy-proven LCH. Analysis was performed on routine brain MRI obtained before or after therapy. Region of interest (ROI) methodology was used to determine ASL cerebral blood flow (CBF) (mL/100 g/min) in the following bilateral regions: angular gyrus, anterior prefrontal cortex, orbitofrontal cortex, dorsal anterior cingulate cortex, and hippocampus. Quantile (median) regression was performed for each ROI location. CBF patterns were compared between pre- and posttreatment LCH patients as well as with age-matched healthy controls. RESULTS: Significantly reduced CBF was seen in posttreatment children with LCH compared to age-matched controls in angular gyrus (P = .046), anterior prefrontal cortex (P = .039), and dorsal anterior cingulate cortex (P = .023). Further analysis revealed dominant perfusion abnormalities in the right hemisphere. No significant perfusion differences were observed in the hippocampus or orbitofrontal cortex. CONCLUSION: Perfusion in specific cerebral regions may be consistently reduced in children with LCH, and may represent effects of underlying disease physiology and/or sequelae of chemotherapy. Studies that combine a formal cognitive assessment and hemodynamic data may further provide insight into perfusion deficits associated with the disease and the potential neurotoxic effects in children treated by chemotherapy.

Robot-assisted versus manual navigated stereoelectroencephalography in adult medically-refractory epilepsy patients.

OBJECTIVE: Stereoelectroencephalography (SEEG) has experienced a recent growth in adoption for epileptogenic zone (EZ) localization. Advances in robotics have the potential to improve the efficiency and safety of this intracranial seizure monitoring method. We present our institutional experience employing robot-assisted SEEG and compare its operative efficiency, seizure reduction outcomes, and direct hospital costs with SEEG performed without robotic assistance using navigated stereotaxy. METHODS: We retrospectively identified 50 consecutive adult SEEG cases at our institution in this IRB-approved study, of which 25 were navigated with image guidance (hereafter referred to as "navigated") (02/2014-10/2016) and 25 were robot-assisted (09/2016-12/2017). A thorough review of medical/surgical history and operative records with imaging and trajectory plans was done for each patient. Direct inpatient costs related to each technique were compared. RESULTS: Most common seizure etiologies for patients undergoing navigated and robot-assisted SEEG included non-lesional and benign temporal lesions. Despite having a higher mean number of leads-per-patient (10.2 ± 3.5 versus 7.2 ± 2.6, P = 0.002), robot-assisted cases had a significantly shorter mean operative time than navigated cases (125.5±48.5 versus 173.4±84.3 min, P = 0.02). Comparison of robot-assisted cases over the study interval revealed no significant difference in mean operative time (136.4±51.4 min for the first ten cases versus 109.9±75.8 min for the last ten cases, P = 0.25) and estimated operative time-per-lead (13.4±6.0 min for the first ten cases versus 12.9±7.7 min for the last ten cases, P = 0.86). The mean depth, radial, target, and entry point errors for robot-assisted cases were 2.12±1.89, 1.66±1.58, 3.05±2.02 mm, and 1.39 ± 0.75 mm, respectively. The two techniques resulted in equivalent EZ localization rate (navigated 88 %, robot-assisted 96 %, P = 0.30). Common types of epilepsy surgery performed consisted of implantation of responsive neurostimulation (RNS) device (56 %), resection (19.1 %), and laser ablation (23.8 %) for navigated SEEG. For robot-assisted SEEG, either RNS implantation (68.2 %) or laser ablation (22.7 %) were performed or offered. A majority of navigated and robot-assisted patients who underwent epilepsy surgery achieved either Engel Class I (navigated 36.8 %, robot-assisted 31.6 %) or II (navigated 36.8 %, robot-assisted 15.8 %) outcome with no significant difference between the groups (P = 0.14). Direct hospital cost for robot-assisted SEEG was 10 % higher than non-robotic cases. CONCLUSION: This single-institutional study suggests that robotic assistance can enhance efficiency of SEEG without compromising safety or precision when compared to image guidance only. Adoption of this technique with uniform safety and efficacy over a short period of time is feasible with favorable epilepsy outcomes.