bluuebunny/crossref_metadata_2025 huggingface dataset:
341 Post-Operative Outcomes and Rare Complications in Pediatric Stereotactic Electroencephalography: A Retrospective Review from a High Volume Pediatric Epilepsy Center
Authors: Plonsker Jillian Hannah , Stone Lauren , Wali Arvin Raj , Daniel Manjari , Ravindra Vijay , Gonda David D. , Khan Usman , Sattar Shifteh
Published: March 2023

INTRODUCTION:

Stereotactic electro-encephalography (sEEG) allows for spatial and temporal localization of epileptic foci for definitive treatment guidance. High volume center studies are more likely to detect rare, although potentially significant complications.

METHODS:

A retrospective review of 58 sEEG cases performed by a single surgeon at a single pediatric academic institution was performed. Patients <18 years old were included. Patients without 5 years of follow-up were excluded.

RESULTS:

25 (49%) of the patients undergoing SEEG were non-lesional on pre-operative imaging. 50 patients (98%) received surgical treatment of their epilepsy following sEEG. 19 underwent open surgical resection of EZ, 16 laser interstitial thermal ablation, 13 responsive neurostimulation, and 1 was treated with DBS. We achieved Engle 1, 2, 3, and 4 level outcomes in 22 (55%), 8 (20%), 5(13%), 5 (13%) of patients respectively. Engle outcome scores were comparable for lesional and non-lesional EZ in patients who underwent resection (Engle 1 outcome in 10/12 and 1/2 respectively) and ablation (6/9 and 6/7, respectively). IPH occurred in 3 cases (5.2%), with only one requiring surgical evacuation. 2 of the 3 hemorrhages caused transient neurologic deficits and the third caused a longstanding hemiparesis. Two (3.4%) cases developed asymptomatic pseudo-aneurysms identified on routine delayed vascular imaging. One was treated successfully with endovascular coiling, however the second was too distal and required surgical clipping. There were no complications from either pseudo-aneurysm treatment.

CONCLUSIONS:

sEEG offers favorable morbidity, source localization, and seizure control in surgical lesions. We recommend surveillance imaging with CTA or MRA 3-6 months post operatively to rule out pseudoaneurysm formation given.
344 Drivers of Adverse 30-Day Outcomes for Pediatric Spine Tumor Surgery Patients: A Nationwide Analysis
Authors: Tang Oliver Young , Chen Jia-Shu , Groves Mari L. , Shao Belinda , Ganga Arjun , Svokos Konstantina , Klinge Petra Margarete , Zadnik Sullivan Patricia Leigh
Published: March 2023

INTRODUCTION:

Spine tumors in children are an uncommon clinical entity. Drivers of reoperation and readmission following surgery for this pathology are poorly characterized.

METHODS:

We conducted a retrospective cohort analysis of all spine tumor surgery cases in the National Surgical Quality Improvement Program-Pediatrics database from 2012-2020, using diagnosis and Current Procedural Terminology codes. The primary outcome was a composite of 30-day mortality, reoperation, readmission, and non-home discharge disposition. Stepwise regression with bidirectional elimination via the Akaike Information Criterion was used to identify predictors of adverse 30-day outcomes. 25 candidate variables were assessed, including tumor characteristics, patient demographics, preoperative comorbidities, operative details, and postoperative complications.

RESULTS:

The analytic cohort included 728 pediatric patients undergoing spine tumor surgery. Patients predominantly had intradural intramedullary tumors (79.3%). Average age was 7.7 years and 54% were male. 86.5% were discharged to home. 30-day mortality rate was 0.4%. 48 patients (6.6%) required reoperation, with the most common reasons being infection (n = 14), repair of cerebrospinal fluid leak (n = 8), shunt placement (n = 8), and tumor recurrence (n = 6). 39 patients (5.4%) underwent readmission within 30 days, primarily for surgical site infection (n = 11), nervous system complication (n = 8), or wound dehiscence (n = 7). Stepwise regression identified predictors of adverse 30-day outcomes including emergent surgery (OR = 2.64, P = 0.014), operative time (OR = 1.03 per +10 minutes, P < 0.001), length of stay (OR = 1.03 per +1 day, P = 0.035), surgical site infection or dehiscence (OR = 5.26, P < 0.001), nervous system complications (OR = 10.31, P = 0.009), and non-surgical site infections (OR = 27.95, P < 0.001). When mortality, reoperation, and readmission were analyzed in aggregate, emergent surgery and postoperative complications remained as significant predictors.

CONCLUSIONS:

30-day adverse events following pediatric spine tumor surgery were predominantly driven by emergent surgery, prolonged operative or hospitalization time, and postoperative complications.
345 Structural Cardiac Defects and Vascular Anomalies in Vein of Galen Malformation Patients: A Multi-Institutional Cohort With Genetic Sequencing
Authors: Piwowarczyk Paulina , Moyer Quentin , Mekbib Kedous Y. , Kappel Ari D. , Zhao Shujuan , Shohfi John , Smith Hannah , Orbach Darren , See Alfred P. , Smith Edward R. , Kahle Kristopher
Published: March 2023

INTRODUCTION:

Vein of Galen malformations (VOGM) are rare, potentially lethal brain arteriovenous malformations (AVM). The roles of EPHB4, RASA1, and ACVRL1 have been described in VOGM pathogenesis, and previous studies have reported the co-occurrence of VOGM with cardiac and vascular disorders.

METHODS:

We queried our cross-institutional cohort of 129 VOGM patients with detailed genotypic and phenotypic data. Genetic samples from a subset of 114 VOGM probands, including 90 trios, underwent whole exome sequencing.

RESULTS:

We found that 9.3% of our patients had structural cardiac defects, as compared to 0.8-1.2% in the general population. Our cohort’s cardiac defects included 3.9% with patent ductus arteriosus, compared to 0.1% in the general population, and 1.6% with atrial septal defect, a congenital condition previously connected to VOGM. 22.5% of our patients had vascular abnormalities, including 16.3% with cutaneous vascular lesions and 4.7% with recurrent epistaxis. One patient presented with VOGM and moyamoya disease. Our whole exome sequencing found that patients with damaging RASA1 mutations presented with significantly more cutaneous vascular lesions relative to the rest of the VOGM cohort (60% vs 16%, p = 0.007) and patients with damaging ACVRL1 mutations had significantly higher rates of recurrent epistaxis (50% vs 5%, p = 0.002).

CONCLUSIONS:

RASA1 is associated with capillary malformation-arteriovenous malformation syndrome (CM-AVM), and ACVRL1 is associated with hereditary hemorrhagic telangiectasia (HHT); CM-AVM and HHT are neurovascular disorders in which the VOGM phenotype is frequently encountered. Our findings demonstrate the high incidence of cardiac defects and vascular abnormalities in VOGM patients and the value of clinical sequencing of VOGM patients with these co-occurring clinical features.
346 Development of Deuterium Magnetic Resonance Imaging for Cerebrospinal Fluid Studies
Authors: Hunt Rachel Joy , Nagaraja Tavarekere , Knight Robert , Lee Ian Yu , Ewing James , Penning Donald
Published: March 2023

INTRODUCTION:

Over the past ten years, the role of the glymphatic system has been defined and explored using various cerebrospinal fluid (CSF) tracers to track the movement of CSF through the perivascular spaces and into the brain interstitium. Glymphatic studies most commonly use gadolinium as a CSF tracer, which is not blood-brain-barrier (BBB) soluble. The primary component of CSF is water, however, which is BBB permeable. Cerebrospinal fluid may behave differently than large molecule tracers. Heavy water (D2O) is an isotope of water often used in physiology studies. We hypothesized that D2O would provide a traceable MR signal in the brain, allowing for more physiologically realistic models of CSF flow within the glymphatic system.

METHODS:

Two adult male rats underwent deuterium enhanced MR imaging. Images were obtained using a custom-made RF transmit/receive coil from Rapid MR International that is dual tuned to both proton (1H, 300.3 MHz) and deuterium (2H, 46.1 MHz) resonant frequencies for use in a 7 Tesla Bruker MRI system. After appropriate system calibration for optimization of deuterium MR signal with intravenous D2O infusion, the rats underwent spinal catheter implantation for intrathecal infusion. Images were taken during and after D2O infusion to evaluate uptake and clearance.

RESULTS:

Deuterium produced a imageable MR signal in the brain with intravenous and intrathecal infusion. Complete signal washout was noted within 10 minutes of stopping the intrathecal infusion.

CONCLUSIONS:

Deuterium MRI holds promise as a physiologic CSF tracer. As the technique is refined, it can be used for further CSF physiology studies. The rapid clearance of intrathecal D2O as compared to previous models using gadolinium supports our theory that CSF behaves differently than the large molecule tracers historically used to characterize its flow.
348 Risk of Rupture and Treatment Outcomes of Giant Pediatric Aneurysms: Multi-Institutional Case Series and Meta-Meta-Analysis
Authors: Gupta Saksham , Hauser Blake Marie , Catapano Joshua , Farhadi Dara , Smith Edward R. , Lawton Michael T. , Du Rose
Published: March 2023

INTRODUCTION:

Giant pediatric aneurysms are vascular malformations that can cause significant neurologic morbidity and mortality. Their rarity has precluded large cohort studies to inform their management.

METHODS:

Multi-institutional cohort study of cases from Boston Children’s Hospital (BCH) and the Barrow Neurologic Institute (BNI) along with systematic review and meta-analysis of previously reported cases.

RESULTS:

A total of 15 patients were included in the multi-institutional cohort, and an additional 88 patients were included from 14 series to yield 103 patients within the meta-analysis. Amongst the BCH patients, male sex was associated with giant size (OR .2; 95% CI 1.2-162.0).The most common aneurysm locations were in the MCA (38%), ICA (25%), vertebral artery (VA; 11%), and VBJ (8%). Within 69 reports containing radiographic data within the meta-analysis, 38% of aneurysms were saccular. Twenty-eight cases presented with rupture (28%). 0% of cavernous ICA aneurysms, 26% of other anterior circulation aneurysms, and 44% of posterior circulation aneurysms presented with rupture. Increasing age (OR 1.2; 95% CI 1.0-1.4) and saccular morphology (OR 5.3, 95% CI 1.5-18.9) were associated with presentation with rupture, while posterior location trended towards an association (OR 3.1, 95% CI 0.9-11.0). The majority of cases in the systematic review were treated (97%) rather than observed (3%). Endovascular and open treatments were utilized in 40 and 56% of cases. Survival was 97% for unruptured aneurysms and 82% for ruptured aneurysms. A favorable neurologic outcome occurred in 80% of unruptured cases and 54% of ruptured cases. Unruptured presentation (OR 3.7, 95% CI 1.3-11.1) and endovascular treatment modality were associated with a favorable outcome (OR 5.0; 95% CI 1.6-15.8).

CONCLUSIONS:

Giant pediatric aneurysms are unlikely to be discovered incidentally and often merit treatment. Increasing age and saccular morphology are r predict rupture, and should elevate the concern for semi-urgent treatment.
355 Robotic and Navigated Pedicle Screws Are Safer and More Accurate than Freehand Screws: A Systematic Review and Meta-Analysis
Authors: Matur Abhijith V. , Duah Henry , Palmisciano Paolo , Chilakapati Sai , Cheng Joseph S. , Adogwa Owoicho
Published: March 2023

INTRODUCTION:

Navigation and robotic pedicle screw placement systems have been developed to improve the accuracy of screw placement. However, the literature comparing the safety and accuracy of robotic and navigated screw placement with freehand screw placement in thoracolumbar spine surgery has been limited.

METHODS:

PubMed and EMBASE were systematically searched according to PRISMA guidelines. The search included indexed terms and text words from database inception to the date of the search (April 7th, 2022). Only randomized controlled trials comparing robotic assisted or navigated screws with fluoroscopic freehand screws in the thoracolumbar spine were included. Data and estimates were pooled using random-effects meta-analysis. Risk of bias was assessed using the Joanna Briggs Institute risk of bias tool. The main outcome measures were odds ratio estimates for screw accuracy according to the Gertzbein-Robbins scale and relative risk for various complications.

RESULTS:

A total of 14 papers encompassing 12 randomized controlled trials were identified. The pooled analysis demonstrated that robotic and navigated pedicle screw placement techniques were associated with increased odds of screw accuracy (OR 2.66, 95% CI 1.24-5.72, p = 0.0118). Robotic and navigated screw placement was associated with a lower risk of facet joint violations (RR 0.09, 95% CI 0.02-0.38, p = 0.0011) and major complications (RR 0.31, 95% CI 0.11-0.84, p = 0.0215). No differences were found in nerve root injury (RR 0.50, 95% CI 0.11-2.30, p = 0.3704), return to the operating room for screw revision (RR 0.28, 95% CI 0.07-1.13, p = 0.0744).

CONCLUSIONS:

These analyses suggest that robotic and navigated screw placement techniques are associated with higher odds of screw accuracy and superior safety profile compared to freehand techniques. Additional randomized controlled trials will be needed to further validate these findings.
361 Awake Spinal Fusion Leads to Decreased Postoperative Opioid Use and Decreased Length of Stay Compared to General Anesthesia: A Matched Cohort Study
Authors: Sykes David , Tabarestani Troy , Chaudhry Nauman Shaukat , Berger Miles , Ayoub Chakib , Gadsden Jeffrey , Gupta Dhanesh Kumar , Shaffrey Christopher I. , Abd-El-Barr Muhammad M.
Published: March 2023

INTRODUCTION:

Over the past several years, there has been increasing interest in performing spinal fusion under awake spinal anesthesia (SA) as an alternative to general anesthesia (GA). The evidence supporting its use has been positive, albeit limited.

METHODS:

The authors performed a retrospective review of a single surgeon’s patients who underwent lumbar interbody fusions under SA vs GA. Each SA patient was compared to a demographically-matched GA counterpart undergoing a comparable procedure by parametric T-tests. Analyzed outcomes include operative time, opioid usage in morphine milligram equivalents (MME), time to ambulation (TTA), and length of stay (LOS).

RESULTS:

8 SA patients were matched to 8 GA counterparts; the cohort had a mean age of 66.8, a mean BMI of 26.4, and a mean American Society of Anesthesiologists Physical Status (ASA-PS) of 2.81. GA and SA patients demonstrated no statistically significant differences in age, BMI, or ASA-PS. All patients received erector spinae plane blocks with 1.3% liposomal bupivacaine. Postoperative opioid use was reduced in SA patients compared to GA patients (18.86 vs 54.34 MME, p = 0.026). SA patients also demonstrated a shorter hospital LOS (0.52 vs 2.63 days, p = 0.029). SA patients did not demonstrate a statistically significant reduction in procedure duration (138 vs 169 minutes, p = 0.207) nor a statistically significantly reduced TTA (3.85 vs 31.33 hours, p = 0.092).

CONCLUSIONS:

These preliminary retrospective results suggest the use of SA rather than GA for lumbar fusions is associated with lower opioid utilization and reduced hospital length of stay. Future randomized prospective studies are warranted to determine if SA usage truly leads to these beneficial outcomes.
365 Awake Spine Surgery for Traditionally Poor Surgical Candidates: An Illustrative Cohort
Authors: Sykes David , Tabarestani Troy , Chaudhry Nauman Shaukat , Berger Miles , Ayoub Chakib , Gadsden Jeffrey , Gupta Dhanesh Kumar , Shaffrey Christopher I. , Abd-El-Barr Muhammad M.
Published: March 2023

INTRODUCTION:

Annually, hundreds of thousands of patients undergo surgery for degenerative spine disease (DSD). This represents only a fraction of patients that present for surgical consideration. Procedures are often avoided due to comorbidities that make patients poor candidates for general anesthesia (GA) and its associated risks. With increasing interest in awake surgery under spinal anesthesia (SA), the authors have observed that SA may facilitate spine surgery in patients with relative contraindications to GA.

METHODS:

Case logs of a single surgeon were reviewed, and patients undergoing spine surgery with SA were identified. Within this group, patients were selected that were only able to receive surgery under SA due to their relative contraindications to GA. For this final cohort, the medical records were consulted to report demographic information, as well as patient outcomes.

RESULTS:

8 patients were identified who were only able to receive lumbar spine surgery for DSD under SA due to their relative contraindications to GA. Comorbidities included octogenarian status, obesity, and chronic health conditions such as Parkinson’s and ischemic heart disease. The cohort was 25% female with a mean age of 72.9, a mean BMI of 30.1 kg/m2, and a mean ASA score of 3.0. The average procedure duration was 142.13 minutes. Mean time to ambulation was 23.18 hours and the average hospital length of stay was 1.67 days. The patients used an average of 28.69 morphine milligram equivalents for pain control in the operative and postoperative days.

CONCLUSIONS:

For patients with symptomatic, refractory DSD and relative contraindications to GA, SA may facilitate safe surgical intervention with excellent outcomes.
371 Activated PPARβ/QKI Signaling in Macrophage/Microglia Sensitizes Glioblastoma to Immunotherapy
Authors: Zeng Ailiang , Hu Jian
Published: March 2023

INTRODUCTION:

Glioblastomas (GBMs) share overwhelmingly immunosuppressive tumor microenvironments that are enriched in glioblastoma-associated macrophages and microglia (GAMs). Notably, GAMs have distinctive reshuffling of lipid composition and dysfunctional lipid metabolism. The peroxisome proliferator-activated receptor (PPAR) family members are master regulators of lipid metabolism in macrophages. One of the PPARs, PPARβ is a pivotal modulator of lipid metabolism in macrophages that orchestrates timely disposal of GBM cells.

METHODS:

Co-immunoprecipitation using an anti-Qki antibody was followed by detecting PPARβ. PPARβ and QKI levels were compared between GAMs inside GBMs and paired macrophages/microglia outside GBMs, as well as human low-grade versus high-grade gliomas. Survival was collected from CX3CR1-CreERT2; PpardL/L/Qki+/+ mice (PPARβ KO) (Ppard is the gene name for PPARβ), CX3CR1-CreERT2; Ppard+/+/QkiL/L mice (QKI KO) and control CX3CR1-CreERT2; Ppard+/+/Qki+/+ (Ctrl) mice given tamoxifen when implanted with GL261 cells. Survival was collected for GBM bearing mice given PPARβ agonist, KD3010 and/or anti-PD-1 therapy.

RESULTS:

PPARβ co-activates the QKI-mediated complex, which is an essential mediator of phagocytosis in macrophage/microglia. Moreover, PPARβ/QKI signaling is markedly decreased in GAMs relative to paired macrophages/microglia within boundary brain parenchyma (P < 0.001). Myeloid cell–specific PPARβ; or QKI knockout shorten overall survival of GBM–bearing mice (P < 0.05), and inhibited PPARβ/QKI signaling in GAMs correlates with grade progression in human gliomas (P < 0.01) and worse prognosis for GBM (P = 0.0034). Therapeutically, PPARβ agonist plus anti-PD-1 greatly prolongs survival of mice GBMs relative to anti-PD-1 monotherapy (P < 0.05).

CONCLUSIONS:

We characterize dysfunctional lipid metabolism in GAMs and elucidates the mechanism underlying immunosuppression of GAMs caused by PPARβ/QKI loss. The study supports for therapeutic options for restoring PPARβ/QKI-mediated lipid metabolism in GAMs and development of novel strategies to sensitize GBM to immunotherapy.
374 Cell Cycle as a Biological Marker of Aggressiveness and Therapeutic Target in Meningiomas
Authors: Lombardi Ismael , Zanini Marco Antonio , Ferrasi Adriana Camargo , Clara Carlos Afonso , Vieira Reis Rui Manuel , Feijó Adriane
Published: March 2023

INTRODUCTION:

Meningiomas are the most common intracranial tumors, accounting for 36% of cases. The World Health Organization (WHO) classifies these tumors into three histological grades: benign (grade I), atypical (grade II) and anaplastic (grade III). Although most lesions are benign, the treatment that is currently widely recommended is restricted to surgery and/or radiotherapy, which are often insufficient for aggressive lesions or lesions that involve neurovascular structures, making the treatment of meningiomas a challenge even today. The understanding of molecular changes in meningiomas may contribute to the identification of aggressiveness markers and possible new therapeutic targets.

METHODS:

The expressions of approximately 800 genes were evaluated, using the PanCancer Nanostring Kit, in 17 meningiomas (6 benign, 6 atypical and 5 anaplastic) and 6 control arachnoids. Comparisons of gene expression between samples of different histological grades and between tumor and control arachnoid samples were performed and the results tabulated in heatmaps after analysis by bioinformatics tools (NSolver, R Statistics, and DAVID, ROSALIND and COSMIC online databases).

RESULTS:

The molecular cell cycle pathway has components upregulated in the three grades of meningiomas analyzed and significantly induced in histologically more aggressive meningiomas. Hyper-regulated genes may be candidates for markers of aggression. In addition, cell cycle induction can be a therapeutic target in more aggressive meningiomas, with the introduction of cell cycle blocking drugs.

CONCLUSIONS:

The hyper-regulated cell cycle pathway may be associated with aggressiveness in meningiomas. Cell cycle induction in meningiomas can be a therapeutic target for the treatment of these tumors, through cell cycle blockers. Additional studies are needed to corroborate the findings of this study.
379 Human Endogenous Retrovirus-K (HML-2) Contributes to a Unique Stem-Cell Niche in Glioblastoma
Authors: Shah Ashish Harish , Rivas Sarah , Doucet-Ohare Tara , Govindarajan Vaidya , DeMarino Catherine , Ampie Leonel , Banasavadi-Siddegowda Yeshavanath , Maric Dragan , Suter Rob , Lee Myoung-hwa , Zaghloul Kareem A. , Walbridge Stuart , Garcia-Montojo Marta , Steiner Joe , Johnson Kory , Gilbert Mark R. , Heiss John D. , Nath Avindra
Published: March 2023

INTRODUCTION:

Human Endogenous Retrovirus (HERV) are ancestral viral relics that comprise nearly 8% of the human genome. Although silenced in normal tissues, the most recently integrated provirus HERV-K (HML-2) can be pathologically reactivated in certain cancers.

METHODS:

We utilized a combination approach using scRNA-seq, multiplex immunofluorescence, and TEM to characterize HERV-K expression in malignant gliomas. Using CRISPR engineering and CHIP-qPCR, we downregulated HML-2 in both patient-derived glioma neurospheres and intracranial orthotopic models and identified interactions between HERV-K and pluirpotency transcription factors.

RESULTS:

We identified pathological expression of HML-2 in human malignant gliomas in CSF (HERV-K DNA/RPP30 = 35.2 ± 8.8 vs 23.1 ± 6.7, n = 18, p = 0.02) and tumors (HERV-K RNA/HPRT mean = 1.15 ± 0.2 vs. 0.5 ± 0.2, p = 0.01, n = 20) compared to epilepsy controls. Aberrant HML-2 expression corresponded to a unique stem-cell niche using multivoxel automated segmentation. Using a tailored scRNA-seq sequencing pipeline, we identified glioblastoma cellular populations with elevated HML-2 transcripts in neural progenitor-like cells that can drive cellular plasticity (ANOVA, p < 0.001). Using CRISPR technology, we demonstrate that HML-2 is critical to maintenance of glioblastoma stemness and tumorigenesis in both glioblastoma neurospheres and intracranial orthotopic murine models (OS: 26 days vs. 18.6, p=0.0008, n=20). Downregulation of HERV-K using CRISPRi reduces the glioblastoma neurosphere formation (2-way ANOVA, p < 0.0001) and HERV-K env, Polymerase, OCT4 and Nestin transcripts (2-way ANOVA p < 0.001). Moreover, using Transmission Electron Microscopy, we discovered that some glioma stem-cells form immature retroviral virions in glioblastoma.

Inhibiting HML-2 expression with nucleoside reverse transcriptase inhibitors reduces extracellular reverse transcriptase (One-way ANOVA, p < 0.05), tumor viability (IC50 = 75.8-123.1 uM), and pluripotency (1-way ANOVA, p < 0.01).

CONCLUSIONS:

Our results suggest that HML-2 is overexpressed in the glioblastoma stem-cell niche. Since persistence of glioblastoma stem-cells is considered responsible for treatment resistance/recurrence, HML-2 may serve as a unique therapeutic target in glioblastoma.
384 Characterization of Ex Vivo and In Vivo Intraoperative Neurosurgical Confocal Laser Endomicroscopy Imaging
Authors: Xu Yuan , Abramov Irakliy , Mignucci-Jiménez Giancarlo , Koskay Grant , Belykh Evgenii , Park Marian , Eschbacher Jennifer , Preul Mark C.
Published: March 2023

INTRODUCTION:

The new FDA-cleared fluorescein sodium (FNa)-based confocal laser endomicroscopy (CLE) imaging system allows for intraoperative on-the-fly cellular level imaging. Two feasibility studies have been completed with intraoperative use of this CLE system in ex vivo and in vivo modalities.

METHODS:

Images acquired from two prospective CLE clinical studies, one ex vivo and one in vivo, were analyzed quantitatively. Two image quality parameters – brightness and contrast – were measured using Fiji software and compared between ex vivo and in vivo images for imaging timing from FNa dose and in glioma, meningioma, and intracranial metastatic tumor cases. The diagnostic performance of the two studies was compared.

RESULTS:

Overall, the in vivo images have higher brightness and contrast than the ex vivo images (p < 0.001). A weak negative correlation exists between image quality and timing of imaging after FNa dose for the ex vivo images, but not the in vivo images. In vivo images have higher brightness and contrast than ex vivo images acquired after FNa redosing. In vivo images have higher image quality than ex vivo images (p < 0.001) in glioma, meningioma, and intracranial metastatic tumor cases. In vivo imaging yielded higher sensitivity (90% vs. 72%) and negative predictive value (81% vs 38%) than ex vivo imaging.

CONCLUSIONS:

In our setting, in vivo CLE optical biopsy outperforms ex vivo CLE by producing higher quality images and less image deterioration, leading to better diagnostic performance. These results support the in vivo modality as the modality of choice for intraoperative CLE imaging.
385 A Cell Resolution Atlas of the Human Cerebrovasculature Reveals Angiogenic and Inflammatory Cell Programs in Arteriovenous Malformations
Authors: Winkler Ethan A. , Kim Chang , Ross Jayden , Garcia Joseph , Gil Eugene , Oh Irene , Chen Lindsay , Wu David , Catapano Joshua , Raygor Kunal P. , Narsinh Kazim , Kim Helen , Weinsheimer Shantel , Cooke Daniel , Walcott Brian Patrick , Lawton Michael T. , Gupta Nalin , Zlokovic Berislav , Chang Edward F. , Abla Adib Adnan , Lim Daniel A. , Nowakowski Tomasz
Published: March 2023

INTRODUCTION:

Coordinated communications between multiple cell types is responsible for cerebrovascular structure and function. Cellular dysfunction results in cerebrovascular diseases, a leading cause of death and disability. However, we lack a complete census of human cerebrovascular cells necessary to advance understanding of disease mechanisms and therapeutic strategies.

METHODS:

To provide a human cerebrovascular cell atlas, we used single-cell RNA sequencing (scRNAseq) to molecularly profile dissociated vascular cells isolated from the adult human brain and AVMs. Joint comparative analyses profiled patterns of aberrant gene expression in AVMs and resolved cell states enriched in AVMs that bled. Results were validated with fluorescent in situ hybridization, immunostaining, and in vitro functional assays

RESULTS:

By performing scRNAseq on 181,388 single-cells, we identified > 40 molecularly-defined vascular or neighboring cell states from the human cerebrovasculature and AVMs. We identified endothelial molecular signatures underlying arteriovenous phenotypic changes known as “zonations.” Our study uncovered an expanded diversity of perivascular cells unique to humans. In AVMs, there was a loss of normal arteriovenous molecular patterning characterized by the emergence of an endothelial cell state with heightened angiogenic potential and immune cell cross-talk within the AVM nidus. We characterized the cellular ontology of cerebrovascular-derived immune cell response and identified infiltration of distinct immune cell states, such as GPNMB+ monocytes, which deplete stabilizing smooth muscle cells in AVMs that bled.

CONCLUSIONS:

Our single-cell atlas highlighted the heterogeneity underlying cell function and interaction in the human cerebrovasculature and defined molecular and cellular perturbations in AVMs, a leading cause of stroke in young people. The identified interplay between vascular and immune cells will aid development of therapeutics targeting angiogenic and inflammatory programs in vascular malformations.
388 Percutaneous Transluminal Angioplasty and/or Stenting for the Treatment of Basilar Artery Stenosis: A Systematic Review and Meta-Analysis
Authors: Palmisciano Paolo , Hoz Samer Saad , Algburi Hagar A. , Ventre Giancarlo Javier , Street Seth , Agyeman Nana , Robinson Michael , Smith Matthew , Shirani Peyman , Grossman Aaron W. , Prestigiacomo Charles J.
Published: March 2023

INTRODUCTION:

Basilar artery stenosis (BAS) carries high morbidity and mortality, with variable outcomes reported after endovascular treatments.

METHODS:

PubMed, EMBASE, Web-of-Science, Scopus, and Cochrane were searched upon the PRISMA guidelines to include studies describing PTAS for BAS. Pooled rates of intervention-related complications and outcomes were analyzed with random-effect model meta-analyses.

RESULTS:

We included 25 studies comprising 1016 patients. Patients were mostly male (79.5%), with hypertension (81.1%) and/or dyslipidemia (56.4%), and presenting with transient ischemic attack (54.4%) or stroke (45.6%). BAS frequently involved the middle basilar artery (51.4%), and were mostly classified as Mori-B (57.4%). PTAS for BAS was indicated in patients with severe (≥50%-70%) symptomatic BAS refractory to dual antiplatelet therapy. Patients underwent angioplasty (95.5%) and/or stenting (92.2%), preferably using Wingspan or Apollo stents. Median baseline BAS was 81% (range, 53%-99%), while median post-intervention BAS was 13% (0%-75%). Actuarial rates of successful intervention and “good” final outcome were 100% (95% CI: 100%-100%) and 89% (95% CI: 85%-93%). Intervention-related recurrent ischemic stroke occurred in 85 patients (8.3%) with actuarial rates of 5% (95% CI: 4%-7%), and was differentiated into perforator (5.4%), in-stent (2.6%), and embolic (0.4%). Actuarial rates of intervention-related dissection, restenosis, and death were 0% (95% CI: 0%-0%), 1% (95%CI: 0%-1%), and 0% (95% CI: 0%-2%).

CONCLUSIONS:

Elective PTAS is safe and effective in selected patients with medically-refractory, severe, symptomatic, and non-acute BAS. Different stent types and angioplasty-assisted procedures should be considered based on specific clinico-radiological characteristics of the lesions.
389 Neutrophils: Novel Contributors to Estrogen-Dependent Intracranial Aneurysm Rupture Via Neutrophil Extracellular Trap Formation
Authors: Patel Devan , Dodd William S. , Lucke-Wold Brandon , Hosaka Koji , Hoh Brian Lim
Published: March 2023

INTRODUCTION:

Intracranial aneurysms (IAs) are more prevalent in women than men and aneurysmal subarachnoid hemorrhage disproportionately affects postmenopausal women. These sex differences suggest estrogen protects against IA progression that can lead to rupture, but the underlying mechanisms are not fully understood. Although studies have demonstrated estrogen regulates inflammatory processes that contribute to IA pathogenesis, the role of neutrophils remains to be characterized.

METHODS:

We compared neutrophil infiltration in C57BL/6 mice that develop IAs to those with a normal circle of Willis. Next, we investigated the role of neutrophils in female estrogen-deficient mice, female estrogen-intact mice, and male mice using a neutrophil depletion antibody. Finally, we studied the role of neutrophil extracellular trap formation (NETosis) as an underlying mechanism of aneurysm progression.

RESULTS:

Mice that developed aneurysms had increased neutrophil infiltration compared to those with a normal circle of Willis. In female estrogen-deficient mice, both neutrophil depletion and NETosis inhibition decreased aneurysm rupture, but not formation, and had no effect on symptom-free survival. In female estrogen-intact mice, neither neutrophil depletion nor NETosis inhibition affected IA formation, rupture, or symptom-free survival. In male mice, neutrophil depletion decreased IA formation but did not affect rupture or symptom-free survival. NETosis inhibition in male mice did not affect IA formation, rupture, or symptom-free survival.

CONCLUSIONS:

Neutrophils contribute to aneurysm rupture in the setting of estrogen deficiency. NETosis appears to be an underlying mechanism for neutrophil-mediated IA rupture in estrogen deficiency. In males, neutrophils contribute to IA formation, but not rupture. Targeting NETosis may lead to the development of novel therapeutics to protect against IA progression, particularly IA rupture in post-menopausal women.
391 Stereotactic Radiosurgery for Intermediate and High-Grade Arteriovenous Malformations: Outcomes Stratified by the Supplemented Spetzler-Martin Grading System
Authors: Naylor Ryan M. , Graffeo Christopher Salvatore , Nesvick Cody L. , Link Michael J. , Brown Paul D. , Stafford Scott , Laack Nadia , Pollock Bruce E.
Published: March 2023

INTRODUCTION:

The Supplemented Spetzler-Martin (Supp-SM) grading system is predictive of surgical risk for patients with brain arteriovenous malformations (AVM).

METHODS:

219 patients had SRS from 1990 to 2016 for SM III (n = 154) or SM IV-V (n = 65) AVM. The Supp-SM grades were 4 (n = 14, 6%), 5 (n = 36, 16%), 6 (n = 67, 31%), 7 (n = 76, 35%), and 8-9 (n = 26, 12%). 60 patients (27%) had deep AVM (basal ganglia, thalamus, or brainstem). 39 patients (18%) had volume-staged SRS; 41 (19%) underwent repeat SRS. The median follow-up was 69 months for grade III AVM and 113 months for grade IV-V AVM.

RESULTS:

163 patients (74%) had obliteration at a median of 38 months after initial SRS. The obliteration rates at 4 and 8 years were 59% and 76%, respectively. 31 patients (14%) had post-SRS deficits from hemorrhage (n = 7, 3%) or radiation injury (n = 24, 11%). 6 patients (3%) died after SRS (hemorrhage, n = 5; radiation injury, n = 1). The rates of neurologic decline or death at 4 and 8 years were 11% and 18%, respectively. Factors predictive of non-obliteration were deep location (HR 0.57, 95% CI 0.39-0.82, p = 0.003) and increasing AVM volume (HR 0.96, 95% CI 0.93-0.99, p = 0.002). Increasing AVM volume was the only factor associated with neurologic decline (HR 1.05, 95% CI 1.02-1.08, p = 0.002). The Supp-SM grading system did not correlate with obliteration (HR 0.94, 95% CI 0.82-1.09, p = 0.43) or neurologic decline (HR 1.15, 95% CI 0.84-1.56, p = 0.38).

CONCLUSIONS:

The Supp-SM grading system was not predictive of outcomes after SRS of intermediate or high-grade AVM. In a cohort which included a high percentage (47%) of “inoperable” AVM (Supp-SM ≥7), most patients had obliteration after SRS, although the chance of neurologic decline was significant.
396 North American Multicenter Experience of the Flow-Redirection Endoluminal Device (FRED) in the Treatment of Intracranial Aneurysms
Authors: Khorasanizadeh MirHojjat , Shutran Max , Schirmer Clemens M. , Salem Mohamed M. , Ringer Andrew J. , Grandhi Ramesh , Mitha Alim P. , Levitt Michael Robert , Jankowitz Brian T. , Taussky Phil , Thomas Ajith J. , Moore Justin M. , Ogilvy Christopher S.
Published: March 2023

INTRODUCTION:

Flow-diverters have revolutionized the endovascular treatment of intracranial aneurysms. The evidence on the Flow Re-direction Endoluminal Device (FRED) is limited compared to some counterparts that have been available for clinical use longer.

METHODS:

Between June 2020 and November 2021, consecutive cerebral aneurysms treated using FRED were included across 7 North American centers. Data collected included patient demographics, aneurysm characteristics, peri-procedural and long-term complications, modified Rankin Scale (mRS) scores, and radiologic follow-up.

RESULTS:

133 aneurysms in 116 patients treated in 123 FRED deployment procedures were included. One hundred twenty-six aneurysms (94.7%) were unruptured, 117 (88.0%) were saccular, and 123 (92.5%) aneurysms were located in the anterior circulation. Mean aneurysm maximal width and neck sizes were 7.2 mm and 4.1 mm, respectively. Successful FRED deployment was achieved in 122 (99.2%) procedures. Radiologic follow-up was available for 101 aneurysms at a median duration of 7.0 months. At the last follow-up, complete occlusion was observed in 55.4%, residual neck in 8.9%, and filling aneurysm in 35.6%. On multivariate regression analysis, age (OR = 0.93; p = 0.001) and aneurysm neck size (OR = 0.83; p = 0.048) negatively correlated with odds of complete occlusion. The retreatment rate was 6/124 (4.8%). The overall complication rate was 31/116 (26.7%). Parent vessel occlusion, covered branch occlusion, and in-stent stenosis were detected in 9/99 (9.1%), 6/63 (9.5%), and 15/99 (15.2%) of the cases, respectively. FRED-related, symptomatic, thromboembolic, and hemorrhagic complication rates were 22.4%, 12.9%, 6.9%, and 0.9% respectively. The morbidity rate was 10/116 (8.6%).

CONCLUSIONS:

As the first large-scale North American multi-center FRED experience, this study confirms FRED’s ease of successful deployment but suggests a lower efficacy and higher rate of complications compared to previous European and South American FRED studies and other flow diverting devices.
397 Direct Carotid Puncture for Mechanical Thrombectomy After Failed Peripheral Access: A Systematic Review and Meta-Analysis
Authors: Domingo Ricardo , Tripathi Shashwat , Abello-Vaamode Jorge , Singh Rohin , Perez-Vega Carlos , Ramos-Fresnedo Andres , Tawk Rabih G.
Published: March 2023

INTRODUCTION:

Direct carotid puncture (DCP) is an alternative route for mechanical thrombectomy (MT), especially in patients with difficult anatomy preventing access through the femoral or radial routes. However, DCP has increased morbidity and mortality due to access site complications related to cervical hematomas.

METHODS:

A systematic search of electronic databases from inception to March 2022 identified 197 related articles for screening. After applying inclusion and exclusion criteria, 10 studies were included, and data was extracted and analyzed using meta-analysis of proportions.

RESULTS:

213 patients were included in this analysis, of which 44% also received intravenous thrombolysis. The overall success rate was 84% (95% CI, 73.66–90.85%; I2 = 25.6%; p = 0.64). The average time to recanalization was 30.33 minutes (95%CI, 23.04–37.62 min; I2 = 89.5%; p < 0.01) and 74% had good reperfusion (TICI >2a) (95% CI, 67–79%; I2 = 0%; p = 0.81). The overall complication rate was 20.38% (95%CI, 15.48–26.35%; I2 = 0%; p = 0.55). The rate of cervical hematomas was 18% (95% CI, 12–16%; I2 = 70%; p = 0.27), of which 24.92% required surgical evacuation (95% CI, 27.5–95.9%; I2 = 70%; p = 0.67). Other reported complications included carotid dissection, pseudoaneurysm, jugular vein puncture, and stroke related to access. The 90-day mortality rate from all causes was 35% based on 7 studies (95% CI, 22.5– 49.9%; I2 = 44.8%; p = 0.08). The mRS at last follow-up was 4.09 (95% CI, 3.68–4.49; I2 = 6.8%; p = 0.37).

CONCLUSIONS:

DCP is a reasonable alternative in patients that fail femoral and radial access for MT and the success rate of access with DCP is 84% with a TICI 2B or TICI 3 achieved in 74% of patients. The complications are mostly related to bleeding at the access site. The high rate of morbidity and mortality warrant further studies to improve the safety of DCP.
400 Availability of Online Second Opinion Services for Spine Surgery: The Market Landscape
Authors: Brown Nolan James , Lien Brian , Gattas Sandra , Sahyouni Ronald , Campos Jessica , Zhang Angie , Reardon Taylor , Singh Rohin , Gendreau Julian , Oh Michael
Published: March 2023

INTRODUCTION:

Second medical opinions may provide patients with a better understanding of their medical condition and empower them to make informed decisions about their health, particularly with respect to surgical treatments. However, the market landscape surrounding “online second opinion” services for spine surgery in the United States is not well-studied.

METHODS:

We utilized Google Trends (i.e., search data since 2010) to ascertain the level of interest in receiving second opinions for spinal surgery. In addition, we contacted the top 30 hospitals for neurology and neurosurgery in the U.S. News rankings by phone to obtain information regarding when/how and at what cost they provide second opinions for spine surgery.

RESULTS:

The cost of the second surgical opinions averaged $493 (±$343) USD (range $90–$1,300); the time to receive a second opinion averaged 20 (±19) days (range 1 day–5 months). Remote or “online second opinion” programs charged an average of $643 (±$259) USD (range $100–$850), and the time to receive an “online second opinion” averaged 14 (±7) days (range 1–4 weeks). We found statistically significant increases in the relative interest for the search term “second medical opinion” over the past decade (P < 0.0001, t = 21.5201). ∼97% of hospitals (29/30) provided in-person consultations for patients seeking a second opinion from a spine surgeon. However, 63% (19/30) did not have remote options (phone/video call consultations or “online second opinions”), but provided in-person consultations as the sole choice.

CONCLUSIONS:

Although second opinions have been shown to be beneficial to patients, ambiguous or high costs and long wait times may serve as barriers for certain groups (i.e., uninsured or underinsured) and potentially diminish the quality of care.
401 Global Neurosurgery Advances from Trenches to Bedside: Lessons from Neurosurgical Care in War, Humanitarian Assistance, and Disaster Response
Authors: Asfaw Zerubabbel , Greisman Jacob , Comunielo Brianna , Zuckerman Scott L. , Etienne Mill , Barthelemy Ernest Joseph
Published: March 2023

INTRODUCTION:

War has influenced the development of neurosurgery. Armed conflict and mass casualty events, including Humanitarian Assistance Disaster Relief (HADR) missions, require military surgeons to innovate to meet extreme demands. Neurosurgeons serving in the military have provided a pragmatic template for global neurosurgeons to emulate in humanitarian disaster responses

METHODS:

We performed a narrative review of the literature examining the influence of wars and mass casualty disasters on contemporary global neurosurgery practices.

RESULTS:

Wartime innovations that influenced global neurosurgery include the development of triage systems and modernization with airlifts, implementation of ambulance corps, early operation on cranial injuries in hospital camps near the battlefield, use of combat body armor, and the rise of damage control neurosurgery. Workforce shortages during wars and disasters have promoted task-shifting and task-sharing in low-resource settings that catalyzed the establishment of the physician associate profession in the United States (US). Neurosurgical care has been utilized by the US as a form of "soft power" during natural and humanitarian disasters. Low-and middle-income countries (LMICs) face similar challenges in developing trauma systems and obtaining advanced technology, including neurosurgical equipment like battery-powered computed tomography scanners. These challenges— ubiquitous in low-resource settings— have underpinned innovations in triage and wound care, rapid evacuation to tertiary care centers, and minimizing infection risk.

CONCLUSIONS:

War and mass casualty disasters have catalyzed significant advancements in neurosurgical care both in the pre-hospital and inpatient settings. Most of these innovations originated in the military with subsequent spread to the civilian sector as military neurosurgeons and civilian neurosurgeons, who are military reservists, returned from the battlefront or other low-resource locations. LMICs have, by necessity, responded to challenges arising from resource shortages by developing innovative, context-specific care paradigms and technologies.
406 Assessing Correlations Between NASS Patient Satisfaction Index and Patient-Reported Outcomes (PROs) at 3-month, 12-month, and 24-month Timepoints in Patients Undergoing Cervical Spine Surgery Using the QOD Registry
Authors: Zaki Mark M. , Joshi Rushikesh Sanjeev , Linzey Joseph Raynor , Strong Michael J. , Yee Timothy Joseph , Saadeh Yamaan S. , Upadhyaya Cheerag D. , Coric Domagoj , Potts Eric A. , Bisson Erica Fay Randy , 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 , Chan Andrew K. , Meyer Scott A. , Asher Anthony L. , Shaffrey Christopher I. , Gottfried Oren N. , Than Khoi Duc , Wang Michael Y. , Buchholz Avery , Haid Regis W. , Park Paul
Published: March 2023

INTRODUCTION:

In value-based healthcare, measuring appropriate outcomes is essential to accurately determine value. Tracked outcomes should reflect the desires of patients undergoing surgical interventions.

METHODS:

The Quality Outcomes Database (QOD), a prospectively collected multi-institutional database, was used to analyze North American Spine Society (NASS) satisfaction, Neck Disability Index (NDI), Visual analog scale for neck pain (NP-VAS) and arm pain (AP- VAS), EuroQoL-Visual Analog Scale (EQ-VAS), and modified Japanese Orthopedic Association (mJOA) at 3, 12, and 24-month follow up.

RESULTS:

1141 patients were surgically treated (anterior approach n = 785, 69%; posterior approach n=356, 31%) for cervical spondylotic myelopathy. Average demographics were 60.5 years old, 52.6% male, 92.4% non-Hispanic, BMI 30.2, and length of stay 2.1 days. At 3 month follow up, satisfaction was positively correlated with NP-VAS (R = 0.298, p<.001), AP-VAS (R = 0.315, p < .001), NDI (R = 0.362, p <.001), and negatively correlated with EQ-VAS (R = -0.294, p<.001) and mJOA (R = -0.287, p < .001). At 12 month follow up, satisfaction was positively correlated with NP-VAS (R = 0.442, p<.001), AP-VAS (R = 0.384, p< .001), NDI (R = 0.459, p < .001), and negatively correlated with EQ-VAS (R = -0.357, p<.001) and mJOA (R = -0.363, p <.001). At 24 month follow up, satisfaction was positively correlated with NP-VAS (R = 0.490, p<.001), AP-VAS (R = 0.358, p < .001), NDI (R = 0.491, p < .001), and negatively correlated with EQ-VAS (R= -0.310, p<.001) and mJOA (R= -0.378, p <.001).

CONCLUSIONS:

NDI was most correlated with satisfaction at 3, 12 and 24-month follow up. mJOA was least correlated with satisfaction at 3 month follow up, whereas EQ-VAS was the least correlated with satisfaction at 12 and 24-month follow up. These findings may better guide outcome selection in patient follow up and help clinicians appropriately counsel patients on expected outcomes.