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John J Kim,1,2 Nathan Buchbinder,1,† Simon Ammanuel,1,4,5,† Robert Kim,1,† Erika Moore,1 Neil O'Donnell,1 Jennifer K Lee,3 Ewa Kulikowicz,3 Soumyadipta Acharya,1 Robert H Allen,1,9 Ryan W Lee,6,7 Michael V Johnston4–81Department of Biomedical Engineering, Whiting School of Engineering, The Johns Hopkins University, 2The James Buchanan Brady Urological Institute, Department of Urology, The Johns Hopkins University School of Medicine, 3Department of Anesthesia and Critical Care Medicine, Johns Hopkins University, 4Kennedy Krieger Institute, 5Hugo W Moser Research Institute, 6Department of Neurology, 7Department of Pediatrics, 8Department of Physical Medicine and Rehabilitation Johns Hopkins University School of Medicine, Baltimore, MD; 9Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA†These authors contributed equally to this workAbstract: Despite recent advances in neonatal care and monitoring, asphyxia globally accounts for 23% of the 4 million annual deaths of newborns, and leads to hypoxic-ischemic encephalopathy (HIE). Occurring in five of 1000 live-born infants globally and even more in developing countries, HIE is a serious problem that causes death in 25%–50% of affected neonates and neurological disability to at least 25% of survivors. In order to prevent the damage caused by HIE, our invention provides an effective whole-body cooling of the neonates by utilizing evaporation and an endothermic reaction. Our device is composed of basic electronics, clay pots, sand, and urea-based instant cold pack powder. A larger clay pot, lined with nearly 5 cm of sand, contains a smaller pot, where the neonate will be placed for therapeutic treatment. When the sand is mixed with instant cold pack urea powder and wetted with water, the device can extract heat from inside to outside and maintain the inner pot at 17°C for more than 24 hours with monitoring by LED lights and thermistors. Using a piglet model, we confirmed that our device fits the specific parameters of therapeutic hypothermia, lowering the body temperature to 33.5°C with a 1°C margin of error. After the therapeutic hypothermia treatment, warming is regulated by adjusting the amount of water added and the location of baby inside the device. Our invention uniquely limits the amount of electricity required to power and operate the device compared with current expensive and high-tech devices available in the United States. Our device costs a maximum of 40 dollars and is simple enough to be used in neonatal intensive care units in developing countries.Keywords: therapeutic hypothermia, evaporative cooling, hypoxic ischemic encephalopathy, birth asphyxia, neuroprotection

Background: Pituitary neoplasms account for 15% of all intracranial neoplasms and affect 20% of the population. Disparities in treatment and outcomes may exist across racial, socioeconomic, and insurance groups, warranting further investigation., Methods: The National Inpatient Sample was analyzed from 2010 to 2020. Pearson's χ 2 test, Fisher's exact test, and independent 2-tailed t-test were used to assess patient characteristics and outcomes. Common complications such as cerebrospinal fluid leak, diabetes insipidus, iatrogenic pituitary disorder, fluid and electrolyte disorders, neurological disorders, pulmonary disorders, and less common complications were assessed. A logistic regression model was used to compare in-hospital mortality and postoperative complications between racial groups. Statistically significant postoperative complications were analyzed with a multivariable logistic regression to determine the independent impact of obesity on postoperative outcomes., Results: Hospitalization rates for this procedure declined significantly over the decade, from 10,279 in 2010 to 5875 in 2020 (trend P value < 0.001). The majority of patients were aged between 25 and 64 years (72.16%), with 60.73% having no comorbidities. While the gender distribution was nearly even, disparities emerged across racial and socioeconomic groups. Black and Hispanic patients were more likely to reside in lower income zip codes and depend on Medicaid compared to White patients. Black patients had higher odds of any postoperative complication (adjusted odds ratio [aOR]: 1.14, P = 0.003) and specific complications like diabetes insipidus, fluid/electrolyte disorders, and renal/urinary issues compared to White patients. Both Black and Hispanic patients faced higher mortality risks postsurgery compared to White patients (aOR: 2.62 and 2.44, respectively, P < 0.05).Medicaid coverage was associated with higher odds of any complication (aOR: 1.18, P = 0.016), while private insurance was linked to lower odds (adjusted OR: 0.88, P = 0.015). Patients in the lowest income quartile had higher odds of complications compared to those in higher quartiles. Obesity independently predicted increased odds of pulmonary, renal, and hemorrhagic complications., Conclusions: Despite advancements in endoscopic endonasal pituitary surgery, disparities in access and outcomes persist across racial, socioeconomic, and insurance groups. These findings underscore the need for targeted interventions to address these inequalities and ensure equitable access to quality care., (Published by Elsevier Inc.)

Background  Multiple nerve transfer techniques are used to treat patients with nerve injuries when a primary repair is not possible. These techniques are categorized to end-to-end, end-to-side, and side-to-side neurorrhaphy. Our study aims to explore the utility of the cross-bridge ladder technique (H-shaped), which has shown promising results in animal models and probably underutilized clinically. Methods  Four patients with significant loss of ankle dorsiflexion were seen in the clinic and underwent evaluation, including electrodiagnostic studies. A cross-bridge ladder repair technique was used between the tibial nerve as the donor and the common peroneal nerve as the recipient via one or two nerve grafts coapted in parallel with end-to-side neurorrhaphies. Dorsiflexion strength was measured preoperatively using the Medical Research Council (MRC) grading system and at each postoperative follow-up appointment. Results  All four patients had suffered persistent and severe foot drop (MRC of 0) following trauma that had occurred between 6 and 15 months preoperatively. Three of the four patients improved to an MRC of 2 several months postoperatively. The last patient had an immediate improvement to an MRC of 2 by his first month and had a complete recovery of ankle dorsiflexion within 4 months from surgery. Conclusion  We demonstrate the utility and clinical outcomes of the cross-bridge ladder technique in patients with persistent and prolonged foot drop following trauma. Both early and late recovery were seen while all patients regained motor function, with some patients continuing to improve up to the most recent follow-up. IRB Approval: Obtained 2013-1411-CP005., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Purpose: In patients with diffuse low-grade glioma (LGG), the extent of surgical tumor resection (EOR) has a controversial role, in part because a randomized clinical trial with different levels of EOR is not feasible., Methods: In a 20-year retrospective cohort of 392 patients with IDH-mutant grade 2 glioma, we analyzed the combined effects of volumetric EOR and molecular and clinical factors on overall survival (OS) and progression-free survival by recursive partitioning analysis. The OS results were validated in two external cohorts (n = 365). Propensity score analysis of the combined cohorts (n = 757) was used to mimic a randomized clinical trial with varying levels of EOR., Results: Recursive partitioning analysis identified three survival risk groups. Median OS was shortest in two subsets of patients with astrocytoma: those with postoperative tumor volume (TV) > 4.6 mL and those with preoperative TV > 43.1 mL and postoperative TV ≤ 4.6 mL. Intermediate OS was seen in patients with astrocytoma who had chemotherapy with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL in addition to oligodendroglioma patients with either preoperative TV > 43.1 mL and residual TV ≤ 4.6 mL or postoperative residual volume > 4.6 mL. Longest OS was seen in astrocytoma patients with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL who received no chemotherapy and oligodendroglioma patients with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL. EOR ≥ 75% improved survival outcomes, as shown by propensity score analysis., Conclusion: Across both subtypes of LGG, EOR beginning at 75% improves OS while beginning at 80% improves progression-free survival. Nonetheless, maximal resection with preservation of neurological function remains the treatment goal. Our findings have implications for surgical strategies for LGGs, particularly oligodendroglioma.

Background: Primary spinal epidural abscess (SEA) is a rare but serious pathology that may result in severe neurologic injury. While certain literature has identified medical risk factors for failure of conservative therapy, no current evidence has been published regarding socioeconomic risk factors associated with failure of medical therapy., Methods: A retrospective review was conducted of patients presenting with SEA from primary spinal infections. Patients presenting with magnetic resonance imaging evidence of SEA treated conservatively in the absence of neurologic deficits were included. Baseline clinical and socioeconomic characteristics were collected. Failure of medical management was defined as requiring surgical intervention despite maximal medical therapy due to the development of neurologic deficits or clinically significant deformity., Results: A total of 150 patients were identified as presenting with magnetic resonance imaging evidence of SEAs without evidence of neurologic deficit. Of these patients, 42 required surgical intervention compared with 108 whose infection was successfully treated with medical therapy alone. Estimated average annual income was $64,746 vs $62,615 in those who successfully cleared their infection with medical management without requiring surgery, which was not statistically significant ( P = 0.5). Insured patients were 5 times more likely to be successfully treated with antibiotics alone compared with uninsured patients (OR = 5.83, P = 0.008). Payer type, employment status, and incarceration status were not associated with failure of conservative therapy., Conclusions: In the treatment of primary SEA, absence of medical insurance is associated with failure of medical management. Payer status, employment status, average salary, and incarceration are not significant risk factors for failure of conservative management., Competing Interests: Declaration of Conflicting Interests : The authors report no conflicts of interest in this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2023 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Objective: To assess the prevalence and clinical implications of variant sciatic nerve anatomy in relation to the piriformis muscle on magnetic resonance neurography (MRN), in patients with lumbosacral neuropathic symptoms., Materials and Methods: In this retrospective single-center study, 254 sciatic nerves, from 127 patients with clinical and imaging findings compatible with extra-spinal sciatica on MRN between 2003 and 2013, were evaluated for the presence and type of variant sciatic nerves, split sciatic nerve, abnormal T2-signal hyperintensity, asymmetric piriformis size and increased nerve caliber, and summarized using descriptive statistics. Two-tailed chi-square tests were performed to compare the anatomical variant type and clinical symptoms between imaging and clinical characteristics., Results: Sixty-four variant sciatic nerves were identified with an equal number of right and left variants. Bilateral variants were noted in 15 cases. Abnormal T2-signal hyperintensity was seen significantly more often in variant compared to conventional anatomy (40/64 vs. 82/190; p = 0.01). A sciatic nerve split was seen significantly more often in variant compared to conventional anatomy (56/64 vs. 20/190; p < 0.0001). Increased nerve caliber, abnormal T2-signal hyperintensity, and asymmetric piriformis size were significantly associated with the clinically symptomatic side compared to the asymptomatic side (98:2, 98:2, and 97:3, respectively; p < 0.0001 for all). Clinical symptoms were correlated with variant compared to conventional sciatic nerve anatomy (64% vs. 46%; p = 0.01)., Conclusion: Variant sciatic nerve anatomy, in relation to the piriformis muscle, is frequently identified with MRN and is more likely to be associated with nerve signal changes and symptomatology.

It can be difficult to avoid violating the pleura during the retropleural approach to the thoracolumbar spine. In this video, the authors resect a short segment of rib to allow more room for pleural dissection during a minimally invasive (MIS) lateral retropleural approach. After a lateral MIS skin incision, the rib is dissected and removed, clearly identifying the retropleural space. The curvature of the rib can then be followed, decreasing the risk of pleural violation. The pleura can then be mobilized ventrally until the spine is accessed. Managing the diaphragm is also illustrated by separating the fibers without a traditional cut through the muscle. The video can be found here: https://stream.cadmore.media/r10.3171/2022.3.FOCVID21138., Competing Interests: Disclosures Dr. Agarwal reports other from Thieme Medical Publishers and Springer Nature, outside the submitted work. Dr. Mummaneni reports personal fees from DePuy Synthes, Globus, and Stryker, outside the submitted work; royalties from DePuy Synthes, Thieme Publishers, and Springer Publishers; and stockholder with Spinicity/ISD. Dr. Chou reports personal fees from Globus and Orthofix, outside the submitted work.Dr. Agarwal reports other from Thieme Medical Publishers and Springer Nature, outside the submitted work. Dr. Mummaneni reports personal fees from DePuy Synthes, Globus, and Stryker, outside the submitted work; royalties from DePuy Synthes, Thieme Publishers, and Springer Publishers; and stockholder with Spinicity/ISD. Dr. Chou reports personal fees from Globus and Orthofix, outside the submitted work., (© 2022, The Authors.)

Background: Biological differences based on sex have been documented throughout the scientific literature. Glioblastoma (GBM), the most common primary malignant brain tumor in adults, has a male sex incidence bias, however, no clinical trial data examining differential effects of treatment between sexes currently exists., Method: We analyzed genomic data, as well as clinical trials, to delineate the effect of sex on the immune system and GBM outcome following immunotherapy., Results: We found that in general females possess enriched immunological signatures on gene set enrichment analysis, which also stratified patient survival when delineated by sex. Female GBM patients treated with immunotherapy had a statistically significant survival advantage at the 1-year compared to males (relative risk [RR] = 1.15; P = .0241). This effect was even more pronounced in vaccine-based immunotherapy (RR = 1.29; P = .0158)., Conclusions: Our study shows a meaningful difference in the immunobiology between males and females that also influences the overall response to immunotherapy in the setting of GBM., (© The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: Fractures in patients with diffuse idiopathic skeletal hyperostosis (DISH) are considered highly unstable injuries with high risk for neurological injury. Surgical intervention is the standard of care for these patients to avoid secondary spinal cord injuries. Despite this, certain cases may necessitate a nonoperative approach. Herein within, the authors describe three cases of cervical, thoracic, and lumbar fractures in the setting of DISH that were successfully treated via orthosis., Observations: The authors present three cases of fractures in patients with DISH. A 74-year-old female diagnosed with an acute fracture of a flowing anterior osteophyte at C6-C7 treated with a cervical orthosis. A 78-year-old male with an anterior fracture of the ankylosed T7-T8 vertebrae managed with a Jewett hyperextension brace. Finally, a 57-year-old male with an L1-L2 disc space fracture treated with a thoraco-lumbo-sacral orthosis. All patients recovered successfully., Lessons: In certain cases, conservative treatment may be more appropriate for fractures in the setting of DISH as an alternative to the surgical standard of care. Most fractures in the setting of DISH are unstable, therefore it is necessary to manage these patients on a case-by-case basis.

Background: Increases in the extent of resection of both contrast-enhanced (CE) and non-contrast-enhanced (NCE) tissue are associated with substantial survival benefits in patients with isocitrate dehydrogenase wild-type glioblastoma. The fact, however, remains that these lesions exist within the framework of complex neural circuitry subserving cognition, movement, and behavior, all of which affect the ultimate survival outcome. The prognostic significance of the interplay between CE and NCE cytoreduction and neurological morbidity is poorly understood., Objective: To identify a clinically homogenous population of 228 patients with newly diagnosed isocitrate dehydrogenase wild-type glioblastoma, all of whom underwent maximal safe resection of CE and NCE tissue and adjuvant chemoradiation. We then set out to delineate the competing interactions between resection of CE and NCE tissue and postoperative neurological impairment with respect to overall survival., Methods: Nonparametric multivariate models of survival were generated via recursive partitioning to provide a clinically intuitive framework for the prognostication and surgical management of such patients., Results: We demonstrated that the presence of a new postoperative neurological impairment was the key factor in predicting survival outcomes across the entire cohort. Patients older than 60 yr who suffered from at least one new impairment had the worst survival outcome regardless of extent of resection (median of 11.6 mo), whereas those who did not develop a new impairment had the best outcome (median of 28.4 mo) so long as all CE tissue was resected., Conclusion: Our data provide novel evidence for management strategies that prioritize safe and complete resection of CE tissue., (Copyright © Congress of Neurological Surgeons 2021. All rights reserved.)

This surgical video demonstrates the technique of an oblique lumbar interbody fusion (OLIF) in the lumbar spine from L2 to L5 as well as an oblique approach to the L5-S1 level. It demonstrates the surgical approach, technical nuances of OLIF, and pearls of the surgery. The video discusses the importance of the release of the disc space to allow for height restoration and deformity correction, endplate preparation to enhance arthrodesis, and appropriate implant sizing. The concept of the approach is the minimally invasive blunt dissection through the abdominal wall musculature and mobilization of the retroperitoneal fat. Unlike the transpsoas approach, the surgery is performed anterior to the psoas, avoiding the lumbar plexus.1 For L5-S1, the approach is still performed in the lateral position but with an oblique approach. A vascular surgeon performs the L5-S1 approach, and the disc space is accessed through the iliac bifurcation.2 The discectomy and interbody fusion are performed similarly to a standard anterior lumbar interbody fusion (ALIF), but in a lateral position and at an oblique angle. The patient consented to this procedure and for filming a video of this case., (© Congress of Neurological Surgeons 2021.)

Objective: A fundamental question in epilepsy surgery is how to delineate the margins of cortex that must be resected to result in seizure freedom. Whether and which areas showing seizure activity early in ictus must be removed to avoid postoperative recurrence of seizures is an area of ongoing research. Seizure spread dynamics in the initial seconds of ictus are often correlated with postoperative outcome; there is neither a consensus definition of early spread nor a concise summary of the existing literature linking seizure spread to postsurgical seizure outcomes. The present study is intended to summarize the literature that links seizure spread to postoperative seizure outcome and to provide a framework for quantitative assessment of early seizure spread., Methods: A systematic review was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A Medline search identified clinical studies reporting data on seizure spread measured by intracranial electrodes, having at least 10 subjects and reporting at least 1-year postoperative outcome in the English literature from 1990 to 2019. Studies were evaluated regarding support for a primary hypothesis: Areas of early seizure spread represent cortex with seizure-generating potential., Results: The search yielded 4562 studies: 15 studies met inclusion criteria and 7 studies supported the primary hypothesis. The methods and metrics used to describe seizure spread were heterogenous. The timeframe of seizure spread associated with seizure outcome ranged from 1-14 seconds, with large, well-designed, retrospective studies pointing to 3-10 seconds as most likely to provide meaningful correlates of postoperative seizure freedom., Significance: The complex correlation between electrophysiologic seizure spread and the potential for seizure generation needs further elucidation. Prospective cohort studies or trials are needed to evaluate epilepsy surgery targeting cortex involved in the first 3-10 seconds of ictus., (© 2020 International League Against Epilepsy.)

Background: Loss-of-function SYNGAP1 mutations cause a neurodevelopmental disorder characterized by intellectual disability and epilepsy. SYNGAP1 is a Ras GTPase-activating protein that underlies the formation and experience-dependent regulation of postsynaptic densities. The mechanisms that contribute to this proposed monogenic cause of intellectual disability and epilepsy remain unresolved., Methods: We established the phenotype of the epileptogenesis in a Syngap1 +/- mouse model using 24-hour video electroencephalography (vEEG)/electromyography recordings at advancing ages. We administered an acute low dose of perampanel, a Food and Drug Administration-approved AMPA receptor (AMPAR) antagonist, during a follow-on 24-hour vEEG to investigate the role of AMPARs in Syngap1 haploinsufficiency. Immunohistochemistry was performed to determine the region- and location-specific differences in the expression of the GluA2 AMPAR subunit., Results: A progressive worsening of the epilepsy with emergence of multiple seizure phenotypes, interictal spike frequency, sleep dysfunction, and hyperactivity was identified in Syngap1 +/- mice. Interictal spikes emerged predominantly during non-rapid eye movement sleep in 24-hour vEEG of Syngap1 +/- mice. Myoclonic seizures occurred at behavioral-state transitions both in Syngap1 +/- mice and during an overnight EEG from a child with SYNGAP1 haploinsufficiency. In Syngap1 +/- mice, EEG spectral power analyses identified a significant loss of gamma power modulation during behavioral-state transitions. A significant region-specific increase of GluA2 AMPAR subunit expression in the somas of parvalbumin-positive interneurons was identified., Conclusions: Acute dosing with perampanel significantly rescued behavioral state-dependent cortical gamma homeostasis, identifying a novel mechanism implicating Ca 2+ -impermeable AMPARs on parvalbumin-positive interneurons underlying circuit dysfunction in SYNGAP1 haploinsufficiency., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and the leading monogenetic cause of autism. One symptom of FXS and autism is sensory hypersensitivity (also called sensory over-responsivity). Perhaps related to this, the audiogenic seizure (AGS) is arguably the most robust behavioral phenotype in the FXS mouse model-the Fmr1 knock-out (KO) mouse. Therefore, the AGS may be considered a mouse model of sensory hypersensitivity. Hyperactive circuits are hypothesized to underlie dysfunction in a number of brain regions in patients with FXS and Fmr1 KO mice, and the AGS may be a result of this. But the specific cell types and brain regions underlying AGSs in the Fmr1 KO are unknown. We used conditional deletion or expression of Fmr1 in different cell populations to determine whether Fmr1 deletion in those cells was sufficient or necessary, respectively, for the AGS phenotype in males. Our data indicate that Fmr1 deletion in glutamatergic neurons that express vesicular glutamate transporter 2 (VGlut2) and are located in subcortical brain regions is sufficient and necessary to cause AGSs. Furthermore, the deletion of Fmr1 in glutamatergic neurons of the inferior colliculus is necessary for AGSs. When we demonstrate necessity, we show that Fmr1 expression in either the larger population of VGlut2-expressing glutamatergic neurons or the smaller population of inferior collicular glutamatergic neurons-in an otherwise Fmr1 KO mouse-eliminates AGSs. Therefore, targeting these neuronal populations in FXS and autism may be part of a therapeutic strategy to alleviate sensory hypersensitivity. SIGNIFICANCE STATEMENT Sensory hypersensitivity in fragile X syndrome (FXS) and autism patients significantly interferes with quality of life. Audiogenic seizures (AGSs) are arguably the most robust behavioral phenotype in the FXS mouse model-the Fmr1 knockout-and may be considered a model of sensory hypersensitivity in FXS. We provide the clearest and most precise genetic evidence to date for the cell types and brain regions involved in causing AGSs in the Fmr1 knockout and, more broadly, for any mouse mutant. The expression of Fmr1 in these same cell types in an otherwise Fmr1 knockout eliminates AGSs indicating possible cellular targets for alleviating sensory hypersensitivity in FXS and other forms of autism., (Copyright © 2019 the authors.)

Objective: Surgical site infection (SSI) following spine surgery causes major morbidity and greatly impedes functional recovery. In the modern era of advanced operative techniques and improved perioperative care, SSI remains a problematic complication that may be reduced with institutional practices. The objectives of this study were to 1) characterize the SSI rate and microbial etiology following spine surgery for various thoracolumbar diseases, and 2) identify risk factors that were associated with SSI despite current perioperative management., Methods: All patients treated with thoracic or lumbar spine operations on the neurosurgery service at the University of California, San Francisco from April 2012 to April 2016 were formally reviewed for SSI using the National Healthcare Safety Network (NHSN) guidelines. Preoperative risk variables included age, sex, BMI, smoking, diabetes mellitus (DM), coronary artery disease (CAD), ambulatory status, history of malignancy, use of preoperative chlorhexidine gluconate (CHG) showers, and the American Society of Anesthesiologists (ASA) classification. Operative variables included surgical pathology, resident involvement, spine level and surgical technique, instrumentation, antibiotic and steroid use, estimated blood loss (EBL), and operative time. Multivariable logistic regression was used to evaluate predictors for SSI. Odds ratios and 95% confidence intervals were reported., Results: In total, 2252 consecutive patients underwent thoracolumbar spine surgery. The mean patient age was 58.6 ± 13.8 years and 49.6% were male. The mean hospital length of stay was 6.6 ± 7.4 days. Sixty percent of patients had degenerative conditions, and 51.9% underwent fusions. Sixty percent of patients utilized presurgery CHG showers. The mean operative duration was 3.7 ± 2 hours, and the mean EBL was 467 ± 829 ml. Compared to nonfusion patients, fusion patients were older (mean 60.1 ± 12.7 vs 57.1 ± 14.7 years, p < 0.001), were more likely to have an ASA classification > II (48.0% vs 36.0%, p < 0.001), and experienced longer operative times (252.3 ± 120.9 minutes vs 191.1 ± 110.2 minutes, p < 0.001). Eleven patients had deep SSI (0.49%), and the most common causative organisms were methicillin-sensitive Staphylococcus aureus and methicillin-resistant S. aureus. Patients with CAD (p = 0.003) or DM (p = 0.050), and those who were male (p = 0.006), were predictors of increased odds of SSI, and presurgery CHG showers (p = 0.001) were associated with decreased odds of SSI., Conclusions: This institutional experience over a 4-year period revealed that the overall rate of SSI by the NHSN criteria was low at 0.49% following thoracolumbar surgery. This was attributable to the implementation of presurgery optimization, and intraoperative and postoperative measures to prevent SSI across the authors’ institution. Despite prevention measures, having a history of CAD or DM, and being male, were risk factors associated with increased SSI, and presurgery CHG shower utilization decreased SSI risk in patients., Abbreviations: ASA = American Society of Anesthesiologists; CAD = coronary artery disease; CHG = chlorhexidine gluconate; CI = confidence interval; DM = diabetes mellitus; EBL = estimated blood loss; LOS = length of stay; MIS = minimally invasive surgery; MRSA = methicillin-resistant Staphylococcus aureus; MRSE = methicillin-resistant Staphylococcus epidermidis; MSSA = methicillin-sensitive S. aureus; MSSE = methicillin-sensitive S. epidermidis; NHSN = National Healthcare Safety Network; OR = odds ratio; SSI = surgical site infection., Competing Interests: Dr. A. K. Chan reports support of non–study-related clinical or research effort from Orthofix. Dr. Dhall reports being a consultant to DePuy Synthes. Dr. Clark reports being a consultant to NuVasive. Dr. Chou reports being a consultant to Medtronic and Globus, and receiving a small royalty from Globus. Dr. Ames reports being a consultant to DePuy Synthes, Medtronic, Stryker, Medicrea, K2M, and Biomet Zimmer; receiving royalties from Stryker, Biomet Zimmer, DePuy Synthes, NuVasive, Next Orthosurgical, K2M, and Medicrea; conducting research for Titan Spine, DePuy Synthes, and ISSG; being on the editorial board of Operative Neurosurgery; receiving grant funding from SRS; being on the Executive Committee of ISSG; and being the director of Global Spine Analytics. Dr. Mummaneni reports being a consultant to DePuy Spine, Globus, and Stryker; direct stock ownership in Spinicity/ISD; receiving statistical analysis for study/writing or editorial assistance on the manuscript from ISSG; receiving support of non–study-related clinical or research effort from the NREF; receiving royalties from DePuy Spine, Thieme Publishing, and Springer Publishing; and receiving honoraria from Spineart.

Virtual Reality (VR) is a powerful tool that has increasingly being used by medical field in recent years. It has been mainly used surgical training in particular laparoscopic procedures. VR can be used for the teaching of anatomy. The aim of the study is to show application of transforming 2D radiologic images into 3D model by using thresholding and segmentation and import into VR interface at an affordable cost. Four anatomy modules are created with inputs to control the rotational and translational movement of 3D models in the virtual space. These movements allow users to explore 3D models by using head tilt and gaze input. 3D models of the Circle of Willis, Vertebral Aneurysm, Spine, and Skull are rendered in the user's field of view at runtime. VR is constructed to have many potentials uses in radiology education. Visualization of 3D anatomic structures in a virtual environment give another tool for teaching to students and patients about anatomy of the body. Four anatomy modules described here demonstrate example user interaction patterns best suited for viewing contexts. Instead viewing stacked 2D images or 3D models confined to desktop applications, virtual reality increases user interactivity of education. An intuitive understanding of anatomic structures in 3D space enhances the learning experience for medical students, residents, and patients we are treating.

Background and Purpose: Idiopathic intracranial hypertension is commonly associated with transverse sinus stenosis, a venous cause of pulsatile tinnitus. In patients with idiopathic intracranial hypertension, CSF drainage via lumbar puncture decreases intracranial pressure, which relieves the stenosis, and may provide at least temporary cessation of pulsatile tinnitus. The objective of this study was to evaluate changes in venous blood flow caused by lowered intracranial pressure in patients with pulsatile tinnitus to help identify the cause of pulsatile tinnitus., Materials and Methods: Ten patients with suspected transverse sinus stenosis as a venous etiology for pulsatile tinnitus symptoms underwent MR imaging before and after lumbar puncture in the same session. The protocol included flow assessment and rating of pulsatile tinnitus intensity before and after lumbar puncture and MR venography before lumbar puncture. Post-lumbar puncture MR venography was performed in 1 subject., Results: There was a lumbar puncture-induced reduction in venous peak velocity that correlated with the opening pressure ( r = -0.72, P = .019) without a concomitant reduction in flow rate. Patients with flow jets had their peak velocity reduced by 0.30 ± 0.18 m/s ( P = .002), correlating with a reduction in CSF pressure ( r = 0.82, P = .024) and the reduction in subjectively scored pulsatile tinnitus intensity ( r = 0.78, P = .023). The post-lumbar puncture MR venography demonstrated alleviation of the stenosis., Conclusions: Our results show a lumbar puncture-induced reduction in venous peak velocity without a concomitant reduction in flow rate. We hypothesize that the reduction is caused by the expansion of the stenosis after lumbar puncture. Our results further show a correlation between the peak velocity and pulsatile tinnitus intensity, suggesting the flow jet to be instrumental in the development of sound., (© 2019 by American Journal of Neuroradiology.)

Stroke is one of the leading causes of death and disability worldwide. Standard treatment for stroke is intravenous (IV) injection of tissue plasminogen activator (t-PA) rapidly after symptom onset. However, there are limitations of IV t-PA treatment, such as a short time window for administration and risk for hemorrhage. Recent trials have demonstrated the benefit of endovascular treatment when added to standard treatment to improve outcomes for patients. Advanced imaging was utilized in some trials to identify patients with proximal intracranial occlusion to target for endovascular reperfusion therapy, and to exclude patients with large infarct cores or poor collateral circulation who would not be expected to benefit from intervention. This article summarizes the use of imaging in recent stroke trials in details, provides a stroke imaging protocol, and provides tips which radiologists should know to help their neurointerventionalists.

Background: Minimally-invasive spine procedures provide targeted, individualized diagnosis and pain management for patients. Competence in these procedures is acquired through experience and training. We created a 3D printed model of a degenerative lumbosacral spine with scoliosis and spondylosis, using materials that mimic bone and soft tissue density under CT. In this study, we evaluate the efficacy of using such a spine model to improve novice trainee confidence and proficiency in performing CT-guided facet joint injections., Results: Thirteen medical students with no prior exposure to CT-guided spine procedures were divided into two groups. Both groups received an introductory didactic lecture, as well as identical pre- and post- test assessments. The Training group (7 students) received two separate training sessions using the simulation model. The Control group (6 students) received only one training session. The Training group demonstrated significantly fewer needle readjustments during the second simulation session, compared with the first session (p = 0.005). Both groups demonstrated significant increase in confidence in ability to perform CT-guided spine procedures on the post-test (p = 0.004 for the Control group and p = 0.00001 for the Training group)., Conclusion: A 3D printed lumbosacral spine phantom with realistic spondylosis can be made to facilitate novice training in minimally-invasive spine procedures. Training using a realistic lumbosacral spine model helps novices acquire the skills and confidence to perform CT-guided spine procedures.

Purpose The aim was to evaluate the impact of protocol changes in selective ophthalmic arterial infusion (SOAI) for treatment of retinoblastoma (Rb). Methods A retrospective review was completed of 35 patients with Rb who were treated with SOAI between March 2010 and January 2017. Treatment details were tabulated for each SOAI session. SOAI protocol was changed in June 2015, and differences before and after this change were evaluated using two-tail chi-square tests and independent sample t-tests to note any differences in technical complications, need for enucleation, and other outcome variables Results 125 SOAI sessions occurred. No technical complications occurred during the study. Two complications (1.6%) occurred in the postoperative setting. Both complications occurred prior to the change in protocol. Comparing the complication rates between the two protocols showed no significant difference (2.2% versus 0.0%; p = 0.505); 29 of 43 (67.4%) eyes had their vision preserved overall. Conclusions SOAI is an effective treatment for Rb. The refined protocol described herein was associated with fewer complications.

While several studies indicate the importance of ephrin-B/EphB bidirectional signaling in excitatory neurons, potential roles for these molecules in inhibitory neurons are largely unknown. We identify here an autonomous receptor-like role for ephrin-B reverse signaling in the tangential migration of interneurons into the neocortex using ephrin-B (EfnB1/B2/B3) conditional triple mutant (TM lz ) mice and a forebrain inhibitory neuron specific Cre driver. Inhibitory neuron deletion of the three EfnB genes leads to reduced interneuron migration, abnormal cortical excitability, and lethal audiogenic seizures. Truncated and intracellular point mutations confirm the importance of ephrin-B reverse signaling in interneuron migration and cortical excitability. A non-autonomous ligand-like role was also identified for ephrin-B2 that is expressed in neocortical radial glial cells and required for proper tangential migration of GAD65-positive interneurons. Our studies thus define both receptor-like and ligand-like roles for the ephrin-B molecules in controlling the migration of interneurons as they populate the neocortex and help establish excitatory/inhibitory (E/I) homeostasis., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Mutations in the transcription factor Forkhead box p1 (FOXP1) are causative for neurodevelopmental disorders such as autism. However, the function of FOXP1 within the brain remains largely uncharacterized. Here, we identify the gene expression program regulated by FoxP1 in both human neural cells and patient-relevant heterozygous Foxp1 mouse brains. We demonstrate a role for FoxP1 in the transcriptional regulation of autism-related pathways as well as genes involved in neuronal activity. We show that Foxp1 regulates the excitability of striatal medium spiny neurons and that reduction of Foxp1 correlates with defects in ultrasonic vocalizations. Finally, we demonstrate that FoxP1 has an evolutionarily conserved role in regulating pathways involved in striatal neuron identity through gene expression studies in human neural progenitors with altered FOXP1 levels. These data support an integral role for FoxP1 in regulating signaling pathways vulnerable in autism and the specific regulation of striatal pathways important for vocal communication., (© 2015 Araujo et al.; Published by Cold Spring Harbor Laboratory Press.)

Sleep problems are commonly reported in Rett syndrome (RTT); however the electroencephalographic (EEG) biomarkers underlying sleep dysfunction are poorly understood. The aim of this study was to analyze the temporal evolution of quantitative EEG (qEEG) biomarkers in overnight EEGs recorded from girls (2-9 yrs. old) diagnosed with RTT using a non-traditional automated protocol. In this study, EEG spectral analysis identified high delta power cycles representing slow wave sleep (SWS) in 8-9h overnight sleep EEGs from the frontal, central and occipital leads (AP axis), comparing age-matched girls with and without RTT. Automated algorithms quantitated the area under the curve (AUC) within identified SWS cycles for each spectral frequency wave form. Both age-matched RTT and control EEGs showed similar increasing trends for recorded delta wave power in the EEG leads along the antero-posterior (AP). RTT EEGs had significantly fewer numbers of SWS sleep cycles; therefore, the overall time spent in SWS was also significantly lower in RTT. In contrast, the AUC for delta power within each SWS cycle was significantly heightened in RTT and remained heightened over consecutive cycles unlike control EEGs that showed an overnight decrement of delta power in consecutive cycles. Gamma wave power associated with these SWS cycles was similar to controls. However, the negative correlation of gamma power with age (r = -.59; p<0.01) detected in controls (2-5 yrs. vs. 6-9 yrs.) was lost in RTT. Poor % SWS (i.e., time spent in SWS overnight) in RTT was also driven by the younger age-group. Incidence of seizures in RTT was associated with significantly lower number of SWS cycles. Therefore, qEEG biomarkers of SWS in RTT evolved temporally and correlated significantly with clinical severity.

Mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (Mecp2) cause most cases of Rett syndrome (RTT). Currently there is no cure for RTT. Abnormal EEGs are found in 100% of RTT cases and are associated with severe sleep dysfunction, the cause of which is not well understood. Mice deficient in MeCP2 protein have been studied and characterized for their neuropathological and behavioral deficits to better understand RTT. With the goal to study the non-ictal EEG correlates in symptomatic Mecp2 KO mice (Mecp2(tm1.1Bird/y)), and determine novel EEG biomarkers of their reported progressive neurodegeneration, we used 24 h video-EEG/EMG with synchronous in-vivo cortical glutamate biosensor in the frontal cortex. We scored the EEG for activity states and spectral analysis was performed to evaluate correlations to the synchronous extracellular glutamate fluctuations underlying Mecp2 inactivation as compared to WT. Significant alterations in sleep structure due to dark cycle-specific long wake states and poor quality of slow-wave sleep were associated with a significant increase in glutamate loads per activity cycle. The dynamics of the activity-state-dependent physiological rise and fall of glutamate indicative of glutamate homeostasis were significantly altered in the KO mice. Colorimetric quantitation of absolute glutamate levels in frontal cortex also indicated the presence of significantly higher levels in KO. This study for the first time found evidence of uncompensated sleep deprivation-like EEG biomarkers that were associated with glutamate homeostatic dysfunction in the Mecp2 KO mice.

Neuroinflammation occurs in acute and chronic CNS injury, including stroke, traumatic brain injury, and neurodegenerative diseases. Microglia are specialized resident myeloid cells that mediate CNS innate immune responses. Disease-relevant stimuli, such as reactive oxygen species (ROS), can influence microglia activation. Previously, we observed that p53, a ROS-responsive transcription factor, modulates microglia behaviors in vitro and in vivo, promoting proinflammatory functions and suppressing downregulation of the inflammatory response and tissue repair. In this article we describe a novel mechanism by which p53 modulates the functional differentiation of microglia both in vitro and in vivo. Adult microglia from p53-deficient mice have increased expression of the anti-inflammatory transcription factor c-Maf. To determine how p53 negatively regulates c-Maf, we examined the impact of p53 on known c-Maf regulators. MiR-155 is a microRNA that targets c-Maf. We observed that cytokine-induced expression of miR-155 was suppressed in p53-deficient microglia. Furthermore, Twist2, a transcriptional activator of c-Maf, is increased in p53-deficient microglia. We identified recognition sites in the 3' untranslated region of Twist2 mRNA that are predicted to interact with two p53-dependent microRNAs: miR-34a and miR-145. In this article, we demonstrate that miR-34a and -145 are regulated by p53 and negatively regulate Twist2 and c-Maf expression in microglia and the RAW macrophage cell line. Taken together, these findings support the hypothesis that p53 activation induced by local ROS or accumulated DNA damage influences microglia functions and that one specific molecular target of p53 in microglia is c-Maf.

Despite recent advances in neonatal care and monitoring, asphyxia globally accounts for 23% of the 4 million annual deaths of newborns, and leads to hypoxic-ischemic encephalopathy (HIE). Occurring in five of 1000 live-born infants globally and even more in developing countries, HIE is a serious problem that causes death in 25%-50% of affected neonates and neurological disability to at least 25% of survivors. In order to prevent the damage caused by HIE, our invention provides an effective whole-body cooling of the neonates by utilizing evaporation and an endothermic reaction. Our device is composed of basic electronics, clay pots, sand, and urea-based instant cold pack powder. A larger clay pot, lined with nearly 5 cm of sand, contains a smaller pot, where the neonate will be placed for therapeutic treatment. When the sand is mixed with instant cold pack urea powder and wetted with water, the device can extract heat from inside to outside and maintain the inner pot at 17°C for more than 24 hours with monitoring by LED lights and thermistors. Using a piglet model, we confirmed that our device fits the specific parameters of therapeutic hypothermia, lowering the body temperature to 33.5°C with a 1°C margin of error. After the therapeutic hypothermia treatment, warming is regulated by adjusting the amount of water added and the location of baby inside the device. Our invention uniquely limits the amount of electricity required to power and operate the device compared with current expensive and high-tech devices available in the United States. Our device costs a maximum of 40 dollars and is simple enough to be used in neonatal intensive care units in developing countries.