bluuebunny/crossref_metadata_2025 huggingface dataset:
1233 A Benchmark for Early Biochemical Success and Long-term Remission After Resection of Corticotroph Adenomas in Cushing Disease
Authors: Catalino Michael P. , Moore Dominic , Ironside Natasha , Kearns Kathryn , Min Le , Lee Vance Mary , Jane John Anthony , Laws Edward R.
Published: March 2024

INTRODUCTION:

In Cushing disease, the definition of success after resection of corticotroph adenomas remains unclear given inconsistent pathology and high recurrence rates despite initial biochemical remission.

METHODS:

We collected 12 years of in-hospital cortisol data after the removal of pathology-confirmed corticotroph adenomas in patients with Cushing disease. A novel cortisol halving time analysis was performed using exponential decay modeling, results were dichotomized a priori, and then applied to an external cohort of patients. Halving time was compared to first post-operative cortisol and nadir cortisol variables by estimating long-term remission and time-to-recurrence using Cox regression modeling and the Kaplan-Meier method.

RESULTS:

A total of 320 patients met inclusion/exclusion criteria for the final analysis, and 26 of those patients developed recurrent disease. Median follow-up time was 2.1 years, although 62 patients had five years or longer follow-up time. Higher first post-operative cortisol and higher nadir were associated with increased risk of recurrence. Patients who had a first post-operative cortisol = 50 µd/dL were 4.1 times more likely to recur than those with a first post-operative cortisol < 50 µd/dL (HR 4.1, 1.8-9.2; p = 0.0003). Halving time was not associated with recurrence (HR 1.7, 0.8-3.8, p = 0.18). Patients with a nadir cortisol =2 µg/dL were 6.6 times more likely to recur than those with a nadir cortisol of < 2 µg/dL (HR 6.6, 2.6-16.6, p < 0.0001).

CONCLUSIONS:

Post-operative nadir serum cortisol is the most important cortisol variable associated with recurrence and time-to-recurrence. Compared to first post-operative cortisol and cortisol halving time, a nadir < 2 µg/dL occurring within the first three post-operative days showed the strongest association with long-term remission.
128 The Sagittal Angle of the Trigeminal Nerve at the Porus Trigeminus is a Radiologic Predictor of Surgical Outcome in Microvascular Decompression for Classical Trigeminal Neuralgia
Authors: Bethamcharla Raviteja , Branstetter Barton F. , Sekula Raymond F.
Published: March 2024

INTRODUCTION:

Classical Trigeminal Neuralgia (cTN) is a facial pain syndrome with specific diagnostic criteria, including paroxysms that last 1-120 seconds, are sharp, stabbing, or electric in character, and are induced by innocuous stimuli. The most commonly accepted cause of cTN is neurovascular compression (NVC) of the proximal cisternal segment of the trigeminal nerve by an adjacent artery. Microvascular decompression surgery (MVD) provides immediate and durable relief in many patients.

METHODS:

Pre-operative MRIs from 300 patients with cTN who underwent MVD were analyzed to identify patients with a hyperacute SATNaPT (defined as less than 3 standard deviations below the mean). The rate of surgical success (pain-free after at least 12 months) was compared between patients with a hyperacute SATNaPT and all other patients.

RESULTS:

Patients without a hyperacute SATNaPT had an 82% likelihood of surgical success, whereas patients with a hyperacute SATNaPT had a 58% likelihood of surgical success (p < 0.05). Patients with a hyperacute SATNaPT who also had no evidence of vascular compression on preoperative MRI had an even lower likelihood of success (29%, p < 0.05).

CONCLUSIONS:

In patients with cTN being considered for MVD, a hyperacute SATNaPT is a negative prognostic biomarker that predicts a higher likelihood of surgical failure. Patients with a hyperacute SATNaPT, particularly those without MRI evidence of vascular compression, may benefit from other surgical treatments or a modification of MVD to adequately address the underlying cause of cTN.
129 Neuroimaging Analysis of Bilateral Thalamic Delivery for Gene Therapy
Authors: Daci Rrita , Shazeeb Mohammed , Owusu-Adjei Thomson Brittany , Mietus Constance Jennifer , Vachha Behroze , Moser Richard P. , Gray-Edwards Heather , Sena-Esteves Miguel , Flotte Terrence , Cataltepe Oguz
Published: March 2024

INTRODUCTION:

Axonal transport from the thalamus (an integrative hub for the entire cortex) has been shown to facilitate widespread gene/protein delivery. Here, we report our neuroimaging experience with bilateral thalamic convection-enhanced delivery of adeno-associated virus (AAV) vectors for GM2 gangliosidoses.

METHODS:

Magnetic resonance imaging (MRI) of eight pediatric patients who underwent bilateral thalamic HEXA/HEXB delivery were retrospectively reviewed. Quantitative three-dimensional volumetric analyses of MRI thalamic signals were used to establish volume of distribution (Vd) versus volume of infusion (Vi). The distance of cannula placement within the thalamus was calculated and validated using the numbers used in the intraoperative ROSA robotic software. Backflow and leakage into surrounding structures were also analyzed.

RESULTS:

Fourteen thalamic injection volumes were considered in the final analysis. Calculated volume of thalamic infusate signal was up to 43.8% (mean = 21.3±13.3) of the thalamic volume. The Vd/Vi ratio ranged from 0.4-2.7 (mean = 1.9±0.7), depending on infusate volume. Diffusate shape was round to slightly ellipsoid in all patients. Backflow and leakage were encountered in 14.3% and 12.5%, respectively, of thalamic injections.

CONCLUSIONS:

This study provides the first in-human quantitative MRI data for intrathalamic infusion. The ideal location for the cannula tip was determined to be between the mediodorsal and lateral dorsal nuclei and the ideal trajectory keeps all of the cannula steps within the thalamic boundaries. We also compare these data to published NHP and our own NHP and sheep data. Overall, the Vd/Vi ratios are lower in human subjects (∼2) than in animal subjects (∼3). We hypothesize that this may be due in part to species specific differences in displacement of extracellular fluid versus infusion volume.
157 Minimally Invasive Treatment of Idiopathic Normal Pressure Hydrocephalus Using the Endovascular eShunt Implant
Authors: Lylyk Pedro , Matouk Charles Christian , Siddiqui Adnan Hussain , Lylyk Ivan , Bleise Carlos , Scrivano Esteban , Lylyk Nicholas Pedro , Antonios Joseph Paul , Beneduce Brandon , Levy Elad I. , Heilman Carl B. , Malek Adel M.
Published: March 2024

INTRODUCTION:

Idiopathic Normal Pressure Hydrocephalus (NPH) is a reversible form of dementia typically treated with ventriculo-peritoneal shunt surgery. Recently we have described the first percutaneous transfemoral transvenous deployment of an endovascular CSF shunt (eShunt® System; CereVasc, Inc., Auburndale, MA, USA) to treat communicating hydrocephalus.

METHODS:

Patients were included after demonstrating >20% gait improvement in lumbar drainage trial. Gait was assessed using Timed Up & Go (TUG) test, cognition using Montreal cognitive assessment (MoCA), and urinary incontinence using Neurogenic Bladder Symptom Score (NBSS). Results were normalized per-patient to pre-treatment scores. A composite outcome score (COS) incorporating TUG/MOCA/NBSS was computed.

RESULTS:

Eleven patients (4 female; mean age 74.8 ± 4.2 years) underwent successful eShunt placement. Follow-up data showed significant improvement in gait by 35.4% at 30-days (n = 6, P < 0.003), 24.8% at 90-days (n = 6, p < 0.03) and by 32.8% at 180-days (n = 4, p < 0.01) compared to baseline. MOCA and NBSS showed significant improvements at 30-days and the COS was significantly improved at all time points (p < 0.005 at 30-, 90- and 180-days). No procedural/delayed hemorrhage or unexpected readmissions were encountered during this early follow-up phase.

CONCLUSIONS:

In elderly patients affected by NPH and its insidious effect on mobility, cognition and urinary continence, these results show that the endovascular eShunt implant can be safely deployed with a favorable risk profile and with rapid and sustained improvements in functional outcome scores.
161 Importance of Hospital Centrality Analysis in Brain Metastasis
Authors: Tong Lilin , Patel Ruchit , Dhand Amar , Bi Wenya Linda
Published: March 2024

INTRODUCTION:

Management of patients with brain metastasis (BrM) is complex and interdisciplinary, with patients transitioning between distinct hospitals within an interconnected network at different points of their disease. Prior neurosurgical health delivery quality studies often analyze hospitals in isolation, negating the complexities of patient journey. A facility’s position in an integrated clinical network may therefore play a critical consideration in patient management and outcomes.

METHODS:

We selected BrM patients using ICD codes from the Healthcare Cost and Utilization Project (HCUP) inpatient and emergency department databases from Massachusetts (2018-2019). Hospitals were separated into quartiles based on connectivity, defined as sum of all weighted ties to other hospitals in MA. We compared patient and hospital characteristics across connectivity quartiles and determined impact of hospital connectivity on all-cause mortality, readmission rates, and length of stay using multivariate regression.

RESULTS:

A total of 4679 BrM patients were mapped across MA. While highly connected hospitals were on average larger than peripheral hospitals (p < 0.001), many highly connected hospitals had a low number of patient beds. Patients who visit highly connected hospitals were more likely to live in large metropolitan areas and higher income neighborhoods, and be covered by private insurance (all p < 0.001). Comorbidity scores and age were not meaningfully different between hospitals of varying connectivity scores. Hospital centrality, but not hospital volume, was inversely associated with mortality and readmissions rate, with highly connected hospitals having a lower risk of death (Q1: 2.4 (1.46-3.83); Q2: 1.6 (1.07-2.29); Q3: 1.4 (1.11-1.86); Q4 (ref)).

CONCLUSIONS:

We demonstrate a vital role for hospital connectedness in impacting BrM patient outcome, independent of hospital volume and patient characteristics. Structural barriers, such as insurance or patient residence, may impede patients from receiving care at highly connected hospitals.
173 Electrical Stimulation Used as an Adjunct to Cervical Spine Fusion in Patients at Risk for Pseudarthrosis
Authors: Wind Joshua James , Lansford Todd , Weinstein Marc , Campbell Peter , Vokshoor Amir A. , Beaumont Andrew , Hassanzadeh Hamid , Radcliff Kris , Aleem Ilyas , Coric Domagoj , Cowgill Ian
Published: March 2024

INTRODUCTION:

Prior studies show that pulsed electromagnetic field (PEMF) stimulation promotes bone healing and can be a valuable tool to help overcome biological deficiencies in patients at risk. The current study further evaluates the adjunct effect of PEMF in subjects undergoing cervical spinal surgery presenting with risk factors for pseudarthrosis.

METHODS:

A prospective multicenter clinical trial (NCT 03177473) was conducted at eleven clinical sites. Subjects undergoing cervical spinal fusion surgery with one or more risk factors for pseudarthrosis were identified for enrollment. Risk factors for pseudarthrosis included multilevel fusion, prior failed cervical spine fusion, diabetes, osteoporosis, or smoking. Subjects undergoing cervical spinal fusion were required to wear the PEMF device for 4 hours/day for 6 months post-op. Fusion status was determined at the 12-month visit using anterior/posterior, lateral, and flexion/extension radiographs and computed tomography (without contrast). NDI, EQ-5D, SF-36, and VAS for neck and arm pain were collected as secondary outcome measures.

RESULTS:

Out of 160 subjects, 144 (90.0%) were graded as fused (all levels) at the 12-month visit. Fusion success was 91.7% (n = 55/60), 89.0% (n = 89/100), and 90.9% (n = 20/22) for subjects with 1, 2+, or 3+ risk factors, respectively. Significant improvements in NDI, SF-36, EQ-5D, VAS-arm and VAS-neck were observed compared to baseline (p < 0.001). A device compliance rate of 85.0% was observed at 3-months and 78.3% at 6-months in subjects who had successful cervical fusion.

CONCLUSIONS:

The PEMF bone growth stimulator device is a valuable tool to aid in fusion healing, especially in challenging populations. Subjects in this study experienced favorable fusion rates of 90% and significant improvement in patient reported outcomes despite having elevated comorbidity and/or complex surgeries.
174 Developing Mixed-Effects Models to Optimize Prediction of Postoperative Outcomes in a Modern Sample of Over 450,000 Patients Undergoing Elective Cervical Spine Fusion Surgery
Authors: Shahrestani Shane , Brown Nolan , Yue John K. , Tan Lee A.
Published: March 2024

INTRODUCTION:

Cervical spine decompression and fusion surgery is commonly used to treat degenerative cervical spine pathologies.However, there is a paucity of high-quality data defining the optimal comorbidity indices specifically in patients undergoing cervical spine fusion surgery.

METHODS:

Using data from 2016–2019, we queried the Nationwide Readmissions Database (NRD) to identify individuals who had received cervical spine fusion surgery. The Johns Hopkins Adjusted Clinical Groups (JHACG) frailty-defining indicator was used to assess patient frailty. To measure the level of comorbidity, Elixhauser Comorbidity Index (ECI) scores were queried. ROC curves were developed utilizing comorbidity indices as predictor variables for pertinent complications such as death, non-routine discharge, top-quartile cost, top-quartile length of stay (LOS), and one-year readmission.

RESULTS:

A total of 453,717 patients were eligible for analysis. Non-routine discharges occurred in 93,961 (20.7%) patients. The mean adjusted all-payer cost for the procedure was $22,573.14 ± $18,274.86 (Top Quartile: $26,775.80) and the mean LOS was 2.7 days ± 4.4 days (Top Quartile: 4.7 days). After surgery, there were 703 (0.15%) mortalities and 58,254 (12.8%) readmissions within one year post-operatively. Models using Frailty+ECI as the primary predictor consistently outperformed the ECI only model with statistically significant p-values, as determined by comparing respective AUCs, for most of the complications assessed. Cost and mortality were the only outcomes for which this was not the case, as Frailty outperformed both ECI and Frailty+ECI in cost (p < 0.0001 for all) and Frailty+ECI preformed as well as ECI alone in mortality (p = 0.10).

CONCLUSIONS:

Our data suggests that Frailty+ECI may most accurately predict clinical outcomes in patients receiving cervical spine surgery. These models may be used to identify high risk populations and patients who may necessitate greater resource utilization.
178 Brains on the Pitch: Investigating the Neurophysiological and Neurocognitive Effects of Repetitive Head Impacts in Adolescent Female Soccer Players During a Single Season
Authors: Orr Taylor , Brett Benjamin , Ryan Kaylin , Schiller Katherine , Rezaie Roozbeh , Salinas Felipe , Shimony Nir , Baughman Brandon , Narayana Shalini
Published: March 2024

INTRODUCTION:

Repetitive exposure to head impact in contact sports has raised concerns for potential long-term structural and functional neurologic effects. This relationship has been minimally explored in female athletes, with conflicting results arising from the limited reports on this topic.

METHODS:

Prospective cohort design with pre- and post-season assessments of neurocognitive function, transcranial magnetic stimulation (TMS), and diffusion tensor imaging (DTI). Neurocognitive battery evaluated processing speed, memory, and executive function domains via computerized (ImPACT) and paper-and-pencil testing. TMS assessments included motor evoked potential onset; interhemispheric conduction times; intercortical and intracortical inhibition. DTI measures included fractional anisotropy (FA) for white matter tracts of interest, including: posterior limb of internal capsule; cortical spinal tract; corpus callosum - selected for common involvement in traumatic brain injury within other studies.

RESULTS:

One player was officially diagnosed with concussion and was included in analysis. Neurocognitive performance was intact relative to same aged peers, and there were no significant differences over the season based on mean reliable change indices (-0.79-0.93). Paired t-test analysis indicated that the TMS measures were not significantly different between the two timepoints. Furthermore, DTI FA values and TMS measures were not notably different pre- versus postseason.

CONCLUSIONS:

In this cohort of high school female athletes, we did not observe significant anatomic, physiologic, or functional effects from repetitive head impacts. Our findings contradict previous studies that showed significant neurophysiologic and neurocognitive changes, even in the absence of clinically-observed concussion. Further research is needed to fully understand the long-term consequences of repetitive head impacts in female athletes and to develop effective strategies for mitigating potential risks.
209 Transcriptomic Analysis of the Post-mortem Brain in Intracranial Atherosclerosis Implicates Interferon Signaling
Authors: Seah Carina , Devarajan Alex , Jurczyszak Denise , Chakka Akash , Huckins Laura , Brennand Kristen , Girgenti Matthew
Published: March 2024

INTRODUCTION:

Intracranial atherosclerotic stenosis (ICAS) is a common cause of ischemic stroke. Stroke patients manifesting symptomatic ICAS often have poor prognoses, including worsened functional outcome, increased morbidity, and mortality. Despite risk factor management, ICAS exhibits a nonlinear rise in incidence with age, with an increase in unstable lipid-rich plaques. Understanding mechanisms of ICAS is crucial to improve clinical outcomes and reduce stroke incidence. Previous studies have demonstrated that intracranial arteries demonstrate different histopathologic profiles compared to extracranial arteries, likely lowering their risk of atherosclerosis. However, these studies are limited to healthy intracranial arteries. Comprehensive multiomic data examining diseased intracranial arteries are limited.

METHODS:

We performed bulk transcriptomic analysis in 4 tissues in a post-mortem brain dataset (N=304), with 34 patients with cerebral atherosclerosis confirmed via autopsy, 90 patients with peripheral atherosclerosis, and 180 controls. Cell type deconvolution was conducted to identify differential expression signatures in 7 neuronal and glial subtypes. To examine interferon response further in glial cells, we generated human induced pluripotent stem cell (hiPSC)-derived astrocytes treated with 3 doses of interferon and performed transcriptomic analysis.

RESULTS:

Cerebral atherosclerosis was significantly (pathway enrichment p<10e-9) associated with interferon signaling compared to peripheral atherosclerosis and controls. Glial cells particularly expressed patterns associated with cerebral atherosclerosis. Astrocytes, oligodendrocytes, excitatory neurons, and endothelial cells were most impacted. In hiPSC-derived astrocytes treated with interferon, we identified upregulation of interferon-inducible genes matching those found in intracranial atherosclerosis in the post-mortem brain, implicating glial reactivity to interferon-related stress.

CONCLUSIONS:

Our study implicates interferon signaling as critical within the development of cerebral atherosclerosis. Protection of the intracranial arteries from atherosclerosis may occur due to reduced expression of interferon-inducible genes. Targeted treatment of cerebral atherosclerosis should consider interferon-signaling modulators.
219 A Proposed Technique for Early Venous Sacrifice as an Alternative to Standard Yasargil Technique for Resection of Cerebral AVM's
Authors: Sack Kenneth , Watson Joseph C. , Al-Inaya Yana , Wellington Jack , Dhaliwal Jazz , Amiri Fariba , Zidaru Ana , Spezzani Chiarra , Lehman Natalia , Borjas Nagheli Fernanda , Martinek Monika , Abdeljabbar Nadine , Bone Matan , Abdulrauf Saleem
Published: March 2024

INTRODUCTION:

This study introduces an alternative technique to the standard Yasargil resection of AVMs.

METHODS:

This 20-year prospective observational study compared the outcomes of 510 consecutive patients undergoing resection of AVM using either the early venous sacrifice technique (test group, n = 206) or a historical control group who underwent AVM resection using standard technique (Yasargil Technique, n = 304).

RESULTS:

The test group had significantly more Grade II (35% vs 30.3%) and Grade III (45.1% vs 38.8%) AVMs, while the control group had significantly more Grade I (40.4% vs 7.8%) AVMs. There was no difference in the number of Grade IV or Grade V AVMs. Overall, the test group presented with higher grade AVMs than the control group. Outcomes analyzed included post-operative stroke (CVA), death, modified Rankin Scale (mRS) score, need for blood transfusion, and incomplete obliteration of the AVM. Patients in the test group were 58% less likely to require blood transfusion compared to control (5.8% vs 13.8%, 58% RRR, NNT = 12.5, p = 0.004). Although not statistically significant, there was a trend toward reduced risk of CVA (RRR = 26%), post-operative mRS = 3 (RRR = 30%), and death (RRR = 51%) in the test group relative to the traditional Yasargil technique.

CONCLUSIONS:

In the proposed technique the number of patients requiring blood transfusions was reduced by 1 for every 12.5 patients treated with the standard technique. The number of patients experiencing poor mRS (>3) was reduced by 1 for every 48.7 patients treated. The number of patients experiencing post- operative CVA was reduced by 1 for every 58 patients treated.
224 Artificial Intelligence-based Decision Support Predicts Requirement for Neurosurgical Intervention in Acute Traumatic Brain Injury: Automated Surgical Intervention Support Tool (ASIST-TBI) Development, Validation and Simulated Prospective Deployment
Authors: Malhotra Armaan K. , Smith Christopher , Shakil Husain , Ackery Alun , Mamdani M. , Nathens Avery , Wilson Jefferson , Colak Errol , Witiw Christopher
Published: March 2024

INTRODUCTION:

Artificial intelligence (AI) model integration into clinical workflow offers potential to optimize decision-support for transfer of acute traumatic brain injury (TBI) patients to appropriate trauma centers.

METHODS:

We retrospectively identified TBI patients from 2005-2021 treated at a quaternary Canadian trauma center. We employed various modeling techniques including principal component analysis, three-dimensional convolutional neural networks, and a transformer-based approach using Vision Transformer (ViT) architecture. Model training, validation, and testing was performed using head CT scans with binary ground truth labels corresponding to whether the patient received neurosurgical intervention witin 72 hours. The finalized model, termed Automated Surgical Intervention Support Tool for TBI (ASIST-TBI), was then deployed in a simulated prospective fashion on consecutive TBI patients at our center between March 2021 - September 2022.

RESULTS:

A dataset of 2,806 trauma patients with acute head CT scans were divided into training, validation, and testing groups; the ViT model exhibited optimal performance. There was accurate prediction of requirement for neurosurgical intervention with an area under the receiver operating curve (AUC) of 0·92, accuracy of 0·87, sensitivity of 0·87, and specificity of 0·88 on the testing cohort. In simulated 18-month prospective deployment, an additional 612 consecutive scans were used to assess the performance of ASIST-TBI. Classification accuracy remained robust with AUC of 0·89, 0·85 sensitivity, 0·84 specificity, and 0·84 accuracy. We manually reviewed false positive and false negative cases to identify reasons for misclassification.

CONCLUSIONS:

We developed a novel deep learning model that accurately predicts requirement for acute neurosurgical intervention using unlabeled TBI scans. ASIST-TBI has potential application to optimize state-wide triage efficiency and care pathways for brain-injured patients.
229 Quantitative Imaging Biomarkers for Risk Stratification of Intracranial Aneurysms
Authors: Veeturi Sricharan , Pinter Nandor , Baig Ammad , Ranghuram Ashrita , Sanchez Sebastian , Samaniego Edgar , Levy Elad I. , Siddiqui Adnan Hussain , Tutino Vincent
Published: March 2024

INTRODUCTION:

Aneurysm wall enhancement (AWE) has emerged as a potential imaging biomarker for risk stratification of Intracranial aneurysms (IAs). Herein, the contrast-enhanced MRI (CE-MRI) exhibits markedly higher intensity on the IA sac as compared to the non-enhanced MRI (NE-MRI). However, currently it is assessed subjectively by clinicians which can introduce subjectivity.

METHODS:

We retrospectively collected 105 IAs with their NE-MRI, CE-MRI and Time-of-flight angiography images. IAs were classified as high or low risk if they had PHASES >5 or ELAPSS >20. We then identified the significantly different RFs and used them to build a logistic regression model for identifying high-risk IAs. We also compared the performance of this model with traditional AWE metrics like CCRatio (Average intensity on the IA sac normalized by the corpus callosum intensity) and CRStalk (Average intensity on the IA sac normalized by the pituitary stalk intensity).

RESULTS:

We found 35 high-risk IAs in the cohort and identified 183 RFs that were significantly different between them. After eliminating collinear RFs, we used 52 RFs to build our final model. We observed that the RF based model vastly outperformed the conventional metrics. In the testing set, we observed that the LR model had a higher accuracy as compared to conventional metrics. We observed that non-uniformity in pre-contrast MRI, homogeneity in post-contrast MRI and the difference in gray level non-uniformity had the highest odds ratios in the LR model.

CONCLUSIONS:

RFs from pre- and post-contrast MRI could identify high-risk IAs better than conventional metrics. This model in combination with 3D visualization could aid in better visualization of VWE and better risk stratification of IAs.
233 Evolutionary Analysis Identifies Early Responsive Macrophage Representing as Anti-tumor Myeloid Cell in Glioblastoma
Authors: Zeng Ailiang , Huntoon Kristin , Kim Betty Y.S. , Hu Jian
Published: March 2024

INTRODUCTION:

Glioblastoma (GBM) has no effective treatments. Although immunotherapy has shown promise in certain cancer types, it has not been effective against GBM, largely due to its highly immunosuppressive tumor microenvironment (TMEs), which is rich in tumor-associated macrophages/microglia (TAMs). TAMs in late-stage GBM contribute to T-cell exhaustion and worsen prognosis, but the role of TAMs in earlier stages of tumor development is unclear.

METHODS:

By employing genetically engineered mouse models and human samples, we used spatiotemporal single-cell transcriptomics to investigate TAM evolution during GBM progression.

RESULTS:

We identified a previously unknown macrophage state, termed early responsive macrophage (ERM), that exhibited antitumoral activity. ERMs were found to be abundant in the early stages of GBM progression and spatially enriched in the invading edges of GBMs. ERMs are characterized by upregulated immune response signatures, particularly pathways related to antigen processing and presentation, as well as genes associated with phagocytosis and chemotaxis. Mechanistically, we identified QKI, a transcriptional co-activator, as a key player that activates antigen processing and presentation and MHCII expression in ERMs. Loss of QKI in TAMs is associated with the transformation of ERMs into exhausted tumor-infiltrating macrophages (TIMs), which promote an immune-suppressive TME. Therapeutically, enhancement of QKI's transcriptional co-factor activity greatly improved the efficacy of immune checkpoint blockade.

CONCLUSIONS:

Our study sheds light on the evolutionary trajectory of TAMs in GBM and presents a novel therapeutic approach to enhance their antitumoral activity, thereby constraining tumor growth.
237 SeeMe: An Automated Methodology to Detect Early Signs of Recovery After Acute Brain Injury
Authors: Mofakham Sima , Cheng Xi , Cleri Nathaniel , Saadon Jordan Raphael , Wang Cassie , Kleyner Robert , Zheng Xuwen , Swarna Sujith , Forohar Ariana , Mikell Charles B.
Published: March 2024

INTRODUCTION:

Assessing the functional state of the brain and predicting recovery after acute brain injury (ABI) remains a major unsolved problem. At present, physicians make predictions using clinical examination, traditional scoring systems, and statistical models, which have significant shortcomings and lack the ability to forecast recovery on an individual basis.

METHODS:

SeeMe is based on analyzing subtle facial expressions in response to auditory commands (i.e., “open your eyes,” “make a smile”) over time and compares the results to a pre-stimulus baseline. These subtle motions are often not detectable by the naked eye. We enrolled 26 comatose ABI patients and 16 healthy volunteers to test this tool. Command-evoked eye-opening movements were compared to clinical observation and the JFK Coma Recovery Scale-Revised (CRS-R).

RESULTS:

In our study, 22 of 26 (85%) patients recovered consciousness during hospitalization after ABI. On average, SeeMe detected command-evoked eye opening ∼9 days before clinical assessment using the CRS-R and ∼3 days before blinded human raters who observed the recorded videos using the naked eye.Using the optimally identified decision threshold, SeeMe demonstrated the following performance metrics on ABI patients with no eye opening to command (auditory CRS subscale = 2): sensitivity = 74.1%, specificity = 66.6%, positive predictive value = 16.8%, and negative predictive value = 96.6%.

CONCLUSIONS:

These findings demonstrate the high predictive performance of SeeMe in assessing consciousness in ABI patients and provide a quantitative tool for studying neural circuits and developing novel therapeutic approaches. SeeMe's ability to detect low-amplitude motor movements opens new avenues for understanding and facilitating recovery of consciousness in patients with ABI.
242 Beyond the Stereotypes: Nurturing Success and Retaining Black Women Neurosurgeons
Authors: Charles Antoinette Jasmine , Duvall Julia , Green Destiny , Umoye Alexis , Flowers Jasmine , Woods GaResia , Potter Tamia , Goodwin C. Rory , Corley Jacquelyn , Williamson Theresa
Published: March 2024

INTRODUCTION:

The underrepresentation of African American women in clinical neurosurgery, with fewer than 50 practicing neurosurgeons in the United States, highlights the significant barriers they face due to the intersection of race and gender. These challenges underscore the need for targeted efforts to recruit, retain, and support Black women in neurosurgery.

METHODS:

The study employed a comprehensive identification process to recruit Black women who identified as neurosurgical trainees or clinical neurosurgeons. Virtual interviews were conducted from January 2021 to May 2021, using structured questions to explore various aspects of the participants' experiences navigating neurosurgery as Black women. A thematic analysis was performed on the recorded and transcribed interviews to identify overarching themes.

RESULTS:

The thematic analysis identified key findings regarding Black women in neurosurgery. Mentorship was crucial, with mentors shaping career paths and fostering confidence. Residency program culture, encompassing faculty diversity, family-oriented values, and gender-specific challenges, significantly influenced experiences. Positive and negative experiences underscored the importance of representation, challenges related to racial biases, and the need for a supportive network. Building an equitable and diverse workplace was deemed vital, requiring actions to improve retention, promote Black women to leadership roles, and reduce hierarchical boundaries. Recommendations included diverse leadership, educational initiatives, and programs supporting aspiring neurosurgeons to enhance Black women's representation.

CONCLUSIONS:

The achievements of trailblazing Black women in neurosurgery showcase progress, yet significant disparities persist due to the intersection of race and gender. By addressing these challenges, support can be provided to enhance representation. The study highlights the importance of diverse leadership, comprehensive initiatives, and recognizing the impact of intersectionality in promoting Black women to leadership roles in neurosurgery.
256 The Neuropathological Basis of Elevated Serum Neurofilament Light Following Experimental Concussion
Authors: Arena John , Smith Douglas , Diaz-Arrastia Ramon , Cullen D. Kacy , Xiao Rui , Harris Danielle , Lynch Cillian , Johnson Victoria
Published: March 2024

INTRODUCTION:

Mild traumatic brain injury (mTBI), or concussion, is a substantial health problem, with up to 15% of patients experiencing persisting symptoms. Identifying patients at risk for a poor outcome or protracted recovery remains challenging. Axonal damage caused by rotational forces is now recognized as an important consequence of injury. Moreover, serum measurement of the neurofilament light (NfL) protein has emerged as a potentially promising biomarker of injury.

METHODS:

A gyrencephalic, porcine model of head rotational acceleration scaled to human mTBI was performed with survival of 48 hr (n = 2), 72 hr (n = 6) and 14 days (n = 4) and compared with shams at 72 hr (n = 1) and 14 days (n = 1). Serum NfL was measured pre-injury and at 40 min, 1.5 hr, 3-4 hr, 8 hr, 18 hr, 24 hr, 2 days, 3 days and 14 days post-injury. Detailed neuropathological assessment was performed including staining for markers of cell death (Fluoro-Jade-C), axonal injury (amyloid precursor protein and NfL), and blood-brain barrier (BBB) disruption (fibrinogen).

RESULTS:

Significant elevations in serum-NfL were identified following mTBI, with a peak at 72hr post-injury. Moreover, increased serum-NfL was detectable out to 2 weeks post-injury. Subsequent quantitative histological examinations demonstrated that axonal pathology was the likely source of elevated serum-NfL. However, the extent of axonal pathology quantified via multiple markers did not correlate strongly with the extent of serum-NfL. Interestingly, the extent of BBB permeability offered more robust correlations with serum-NfL measured at multiple time points, suggesting BBB disruption is an important determinant of serum biomarker dynamics after mTBI.

CONCLUSIONS:

These data provide novel insights to the temporal course and pathological basis of serum NfL measurements that inform its utility as a biomarker in mTBI. The ability of NfL to measure underlying pathology will be critical for future clinical and translational research.
275 Absence of Hindbrain Herniation in Myelomeningocele Myeloschisis: A Closer Look at Patients Who Progress to Hindbrain Herniation in the Prenatal and Postnatal Period
Authors: Flanders Tracy Ma , Punchak MSCE; Maria , Land Sierra , Flohr Sabrina , Reynolds Tom , Schmidt Katie , Ertz Danielle , Moldenhauer Julie , Adzick N. Scott , Heuer Gregory G.
Published: March 2024

INTRODUCTION:

Prenatal repair is the gold standard for appropriate patients with fetal myelomeningocele/myeloschisis. Hindbrain herniation is a prerequisite for fetal repair; however, there is a subset of patients without herniation on initial imaging and then progress to herniation on subsequent prenatal/postnatal imaging.

METHODS:

From July 2016 to July 2022, patients seen at the Center of Fetal Diagnosis and Treatment for myelomeningocele/myeloschisis were evaluated for hindbrain herniation. The osseous lesion level was defined as the bony defect level on prenatal ultrasound. Prenatal sac volume was measured on MRI. Prenatal ventricular size was determined on US. The fronto-occipital horn ratio was measured on the first postnatal US.

RESULTS:

Of 422 patients identified with a prenatal diagnosis of myelomeningocele/myeloschisis, 73 were identified who initially had negative hindbrain herniation; of these, 9 and 11 patients progressed to herniation on subsequent prenatal and postnatal imaging, respectively; 32 remained without herniation throughout the prenatal/postnatal period. Sac volume was significant (p = 0.04) for those whose hindbrain herniation was detected on subsequent prenatal visits but not for those diagnosed in the postnatal period (p = 0.10). The majority of patients with hindbrain herniation progression had L1-2 lesions. A subset of patients ultimately underwent permanent CSF diversion (no herniation: 21.8%, prenatal herniation: 33.3%, postnatal herniation: 36.3%).

CONCLUSIONS:

Patients who initially exhibit no hindbrain herniation and then ultimately progress to herniation in subsequent prenatal or postnatal evaluation are more likely to have higher levels of osseous defect. Sac volume was determined as significant for delayed prenatal progression of hindbrain herniation. Further long-term outcomes are necessary to better characterize this unique cohort of patients.
288 Impact of Disc Degeneration on Clinical Outcomes After Fusion for Grade 1 Spondylolisthesis: A 5-year QOD Study
Authors: Yee Timothy Joseph , Upadhyaya Cheerag D. , Coric Domagoj , Potts Eric A. , Bisson Erica Fay , Turner Jay D. , Knightly Jack , Fu Kai-Ming G. , Foley Kevin T. , Tumialan Luis Manuel , Shaffrey Mark Edwin , Bydon Mohamad , Mummaneni Praveen V. , Chou Dean , Kai-Hong Chan Andrew , Meyer Scott A. , Asher Anthony L. , Shaffrey Christopher I. , Gottfried Oren N. , Than Khoi Duc , Wang Michael Y. , Lee Buchholz Avery , Haid Regis W. , Glassman Steven D. , Park Paul
Published: March 2024

INTRODUCTION:

Disc degeneration with loss of disc height can be an indication to fuse patients with lumbar spondylosis. However, its relevance for spondylolisthesis is unknown.

METHODS:

The Quality Outcomes Database was queried for adult patients who underwent fusion for single-level degenerative grade 1 lumbar spondylolisthesis. Pfirrmann grade at the level to be fused was assessed on preoperative sagittal T2-weighted MRI. VAS-back pain (BP-VAS), VAS-leg pain (LP-VAS), and ODI were collected preoperatively and at 3, 12, 24, 36, and 60 months postoperatively.

RESULTS:

The query returned 395 patients. Mean age (95% CI) was 60 (58.9-61.1) years; 39.5% were male. None had a Pfirrmann grade 1 disc. One (0.3%) had a grade 2 disc, 53 (13.4%) had a grade 3 disc, 245 (62%) had a grade 4 disc, and 96 (24.3%) had a grade 5 disc. Posterior-only approach was performed in 92.6%; interbody graft was placed in 92.7%. Mean BP-VAS (95% CI) at baseline, 3 months, 12 months, 24 months, 36 months, and 60 months were 7.1 (6.8-7.3) (n = 343), 3.1 (2.8-3.3) (n = 353), 2.9 (2.6-3.2) (n = 305), 3.2 (2.8-3.5) (n = 283), 3.5 (2.9-4.1) (n = 107), and 3.7 (3.3-4.0) (n = 324). Mean LP-VAS (95% CI) were 6.7 (6.4-7.0) (n = 392), 2.3 (2.0-2.6) (n = 353), 2.2 (1.9-2.6) (n = 306), 2.6 (2.2-2.9) (n = 284), 2.8 (2.2-3.4) (n = 107), and 2.8 (2.4-3.1) (n = 322). Mean ODI (95% CI) were 49.4 (47.8-51.1) (n = 392), 27.4 (25.3-29.5) (n = 347), 22.9 (20.6-25.2) (n = 313), 22.4 (20.1-24.8) (n = 291), 22.4 (18.3-26.4) (n = 97), and 25.9 (23.7-28.2) (n = 325). Utilizing linear regression, Pfirrmann grade was not associated with improvements in VAS-BP, VAS-LP, or ODI at any time point in unadjusted and adjusted analyses (p > 0.05).

CONCLUSIONS:

Patients who undergo fusion for single-level grade 1 spondylolisthesis are likely to experience significant and sustained improvements in pain and function regardless of severity of disc degeneration.
299 Predictors of Unplanned Readmission in Patients Undergoing Intracranial Tumor Resection: A Multi-center Analysis of 31,776 Patients
Authors: Zohdy Youssef M. , Skandalakis Georgios P. , Kassicieh Alex James , Rumalla Kavelin , Kazim Syed Faraz , Schmidt Meic H. , Bowers Christian
Published: March 2024

INTRODUCTION:

Although unplanned readmission is a postoperative outcome metric associated with significant morbidity and financial burden, precise assessment tools for its prediction are yet to be developed. The Revised Risk Analysis Index (RAI) has been recently endorsed as a robust frailty index for predicting surgical outcomes. Hence, the RAI could potentially be utilized to help improve prediction unplanned readmission in patients undergoing intracranial tumor resection (ITR).

METHODS:

Data of patients undergoing ITR were obtained from the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database from the years 2012-2019 using the ICD-9 and ICD-10 codes, indicating ITR. Baseline characteristics, preoperative clinical status, and outcomes were compared between patients with and without unplanned readmission. Frailty, as a measure of baseline physiological reserve, was calculated using the RAI. Univariate and multivariate logistic regression analyses were performed to identify independent associations between unplanned readmissions and patient characteristics.

RESULTS:

The unplanned readmission rate of this cohort (N = 31,776) was 10.8% (N = 3,420). Among the readmitted patients, 958 required unplanned reoperation. Multiple characteristics were significantly different between the readmitted and non-readmitted patients, including age, BMI, comorbidities, and RAI groups (p < 0.05). The most common causes of unplanned readmission were infection (9.4%), seizures (6%), and pulmonary embolism (4%). Patient characteristics identified as reliable predictors of unplanned readmission, included age, body mass index (BMI), functional status, diabetes, hypertension, hyponatremia, and their RAI score (p < 0.05). In multivariate analysis, RAI “frail” patients had an unplanned readmission odds ratio (OR) of 1.3(95%CI; 1.2-1.4), and RAI “severely frail” patients had an OR of 1.6 (95%CI; 1.3-2.1) (p < 0.001).

CONCLUSIONS:

The RAI is a reliable pre-operative frailty index for predicting unplanned readmission following ITR. Utilizing the RAI to identify high risk patients may decrease unplanned readmission through implementation of appropriate management guidelines.
301 Even Heterozygous Loss of CDKN2A B Greatly Accelerates Recurrence in Aggressive Meningioma
Authors: Basit Khan A. Basit , English Collin , Chen William , Athukuri Prazwal , Bayley James , Brandt Vicky , Shetty Arya , Hadley Caroline , Choudhury Abrar , Lu Hsiang-Chih , Harmanci Arif , Harmanci Akdes , Magill Stephen T. , Raleigh David R. , Klisch Tiemo , Patel Akash J.
Published: March 2024

INTRODUCTION:

In the WHO 2021 criteria, homozygous deletion of cyclin-dependent kinase-inhibitor 2A and/or B (CDKN2A/B) qualifies meningiomas as Grade 3. We assessed the effect of heterozygous CDKN2A/B loss, which was not addressed by the WHO, on recurrence-free survival (RFS), and evaluated the relationship of CDKN2A/B losses with our MenG classification.

METHODS:

Methylation and RNA-profiling were used to assign MenG. Methylation data identified heterozygous or homozygous loss of CDKN2A/B in 776 meningiomas. Clinical data for 659 tumors were used for survival analysis.

RESULTS:

Of the 776 tumors, 738 (95.1%) had intact CDKN2A/B, 20 (2.5%) had heterozygous loss of both CDKN2A/B, 3 (0.4%) had homozygous CDKN2A and heterozygous CDKN2B loss, and 15 (1.9%) had homozygous loss of both CDKN2A/B. Of the 659 tumors with clinical data, 28 (4.2%) showed any CDKN2A/B loss. RFS was based on concordant CDKN2A/B status. Tumors with intact CDKN2A/B (n = 631, mRFS not reached) had improved RFS compared to those with heterozygous loss (n = 15, mRFS = 29.1 mo) and homozygous loss (n = 11, mRFS = 10.5mo; p < 0.0001 all groups, homozygous vs. heterozygous p = 0.4, Log-rank). Nearly all tumors with CDKN2A/B loss (27/28) were MenG C, the most aggressive group. Among MenG C tumors, presence of either homozygous (n = 11, mRFS 10.5mo) or heterozygous (n = 14, mRFS 25.1 mo) CDKN2A/B loss led to shortened RFS than those with intact CDKN2A/B (n = 198, mRFS 61.4 mo; p < 0.0001 Log-rank). Median RFS was not reached in MenG A (n = 173) or MenG B (n = 259). Tumors with any CDKN2A/B loss had worse survival when controlling for WHO Grade (Grade: 2 p < 0.0001, 3 p = 0.035, Log-rank).

CONCLUSIONS:

Heterozygous CDKN2A/B loss (not addressed in the 2021 WHO criteria) leads to poor outcome in meningioma even when controlling for molecular subgroup (MenG C) or WHO grade (2/3). All but 1 tumor (27/28) with any type of CDKN2A/B loss were MenG C.
322 A Cost Analysis of Medical Students Applying to Neurological Surgery Residency: An Analysis of the Texas STAR Database
Authors: Lucke-Wold Brandon
Published: March 2024

INTRODUCTION:

Medical Students applying to competitive residencies such as neurosurgery incur substantial costs associated with interviews, away rotations, and application fees. Researchers in the past have examined the sources of expenses during the residency application cycle, but few studies have compared the expenses prior to and during the COVID-19 pandemic.

METHODS:

The TEXAS STAR database was surveyed for applicants of neurosurgical residency programs during the COVID-19 pandemic (2021) and post-pandemic (2022). In total, 66 applicants for the 2021 application cycle and 50 applicants for the 2022 application cycle completed the survey. We compared the application fees, away rotations cost, interview cost, and total expenses as reported by the neurosurgery applicants of the 2021 and 2022 application cycle. A Shapiro-Wilk test was used to test for data normality, and a Mann-Whitney U-Test was used to compare costs during the 2021 and 2022 neurosurgery application cycle.

RESULTS:

There was a statistically significant reduction in total expenses in 2021 vs 2022 ($3,934 vs $9,860). Interview expenses and away rotation expenses were also decreased in 2021 vs 2022 (interview expenses $786 vs $4511, away rotation $1,083 vs $3,000, p < 0.001). Application fee expenses were not different between the 2021 and 2022 application cycle. Regional stratification revealed the greatest reduction in cost, an $11,908 savings, in the South region for the year of 2021.

CONCLUSIONS:

Our study revealed that the COVID-19 pandemic caused a significant reduction in the total fees associated with the neurosurgical residency application. The use of virtual platforms in place of in-person interviews could lessen the financial burden on applicants and alleviate socioeconomic barriers in the neurosurgical application process even after COVID-19.