bluuebunny/crossref_metadata_2025 huggingface dataset:
479 Chronic Subdural Hematomas Treated With Surgical Evacuation Versus Standalone Middle Meningeal Artery Embolization: Volumetric Resolution in Immediate, Early and Late Follow-Up in a Propensity Matched Cohort
Authors: Housley Steven B. , Monteiro Andre , Khawar Wasiq , Donnelly Brianna , Lian Ming , Fritz Alexander , Baig Ammad , Waqas Muhammad , Cappuzzo Justin Mark , Snyder Kenneth Vincent , Siddiqui Adnan Hussain , Levy Elad I. , Davies Jason
Published: March 2023

INTRODUCTION:

Literature comparing surgery and middle meningeal artery embolization (MMAE) for chronic subdural hematomas (cSDH) is limited by patient selection bias. Furthermore, most studies do not perform volumetric measurements over time when comparing these two modalities.

METHODS:

Retrospective search of our database to include cSDH patients managed with either SEA or standalone MMAE. Propensity-score-matching was performed for axial and coronal lengths, maximum diameter and midline shift. Volumes of cSDH were measured at 24 h post-procedure, 3-12-weeks, 12-24-weeks, 24-36-weeks, 36-48-weeks and 48-60-weeks.

RESULTS:

Forty-eight matched hematoma pairs were obtained. The groups were also similar in demographics, comorbidities, medications and symptoms. Median volume was significantly lower at 24 h in the SEA group (SEA, 12.6 mL vs MMAE, 52.7 mL, P < 0.001). Median volume reduction was significantly greater in the SEA group at 24 h (SEA, 39.1 mL vs MMAE, 8.8 mL, P < 0.001) and in the 3-12 weeks interval (SEA, 50.8 mL vs MMAE, 23.7 mL, P < 0.001). The SEA group had significantly greater median resolution rate at 24 h (39.1 mL/day vs 8.8 mL/day, P < 0.001) and in the 3 to 12 weeks interval (1 mL/day vs 0.4 mL/day, P < 0.001) but not in remaining intervals. Near complete resolution at the 3 to 12 interval (SEA, 26.1% vs MMAE, 28%, P = 1) and 12 to 60 weeks interval (SEA, 78.3% vs MMAE, 80%, P = 1) was not significantly different between the groups. Overall, the recurrence was significantly higher in the SEA group than in the MMAE group (22.9% vs 4.2%, P = 0.01).

CONCLUSIONS:

In comparable cSDH patients, surgical evacuation resulted in better volumetric outcomes in the immediate and early follow-up periods but in extended follow-up intervals. Furthermore, surgical patients experienced a significantly higher rate of recurrence.
490 Beyond Placement of Pedicle Screws - New Applications for Robotics in Spine Surgery: A Multi-Surgeon, Single-Institution Experience
Authors: Tabarestani Troy , Sykes David , Murphy Kelly Ryan , Wang Timothy Y. , Shaffrey Christopher I. , Goodwin C. Rory , Horne Phillip , Than Khoi Duc , Abd-El-Barr Muhammad M.
Published: March 2023

INTRODUCTION:

Interest in robotic-assisted spine surgery has grown as surgeon comfort and technology have evolved to maximize the benefits of time-saving and precision. However, the Food and Drug Administration (FDA) has currently only approved robotics to assist in determining the ideal trajectory for pedicle screw placement after extensive research supporting its efficacy and efficiency. To be considered a durable and effective option, robotics need to expand beyond the indication of just placing pedicle screws.

METHODS:

We will explore accessing Kambin’s Triangle in percutaneous transforaminal interbody fusion (percLIF), iliac fixation in metastatic cancer, and sacroiliac (SI) fusions. Each of these topics will be covered in-depth with associated background information and subsequent discussion.

RESULTS:

Without the need for laminectomies or facetectomies, minimal tissue disruption was attained by using RA instrumentation finely tuned to each patient’s unique spinal landscape for percLIF. In the cases of iliac fixation, the use of S2AI screws was precluded by the extensive damage to the sacrum. Therefore, a modified iliac screw entry point was utilized with an entry point slightly more medial than the traditional method, with a pre-planned trajectory of the screws using robot assistance. For SI joint fusion, we review our group at Duke University's published case series displaying the “off-label” use of the robot, which is the first reported case series of its kind in the literature.

CONCLUSIONS:

We show that with a proper understanding of its limitations, robots can help surgeons perform difficult surgeries in a safe manner.
492 Periprocedural Polypharmacy in Lumbar Fusions Performed Under Spinal Anesthesia Compared to General Anesthesia
Authors: Olmos Michelle , Hernandez Nicholas , Kanter Matthew , Liu Penny , Riesenburger Ron I. , Kryzanski James
Published: March 2023

INTRODUCTION:

Lumbar spinal surgery is most often performed under general endotracheal anesthesia (GEA), however spinal anesthesia (SA) is a safe and effective alternative. Postoperative cognitive dysfunction (POCD) is a complication of GEA and the risk of POCD is associated with anesthetic modality and perioperative polypharmacy. Despite the many benefits of SA described in the literature, its efficacy in decreasing polypharmacy has not yet been determined.

METHODS:

Demographic and procedural data of 424 patients undergoing single TLIF via GEA (n = 186) and SA (n = 238) were extracted from our institution’s electronic medical record. We investigated perioperative medication types, number of intraoperative hypotensive episodes, vasopressor requirement, and overall number of perioperative medications used between the two patient groups.

RESULTS:

The number of perioperative medications differed significantly between the two cohorts with the SA cohort receiving a mean of 4.5 medications and the GEA cohort receiving a mean of 10.5 medications (p < 0.0001).This reduction in perioperative medications remained significant after a multivariable analysis to control for confounders (p < 0.001 for all variables). Use of vasopressors was significantly reduced in the SA cohort (p < 0.001), which coincided with a significant reduction in hypotensive episodes in the SA cohort (p < 0.001). Patients undergoing TLIF via GEA had 3.6 times greater odds of experiencing a hypotensive episode intraoperatively (OR = 3.62, 95% CI [2.38-5.49]).

CONCLUSIONS:

Spinal anesthesia is associated with a significant decrease in perioperative medications, including lower vasopressor requirements. We postulate that SA may confer superior intraoperative hemodynamic stability which lowers pressor requirements. The decrease of perioperative medications may be an important contribution in reducing the incidence of POCD in patients undergoing TLIFs.
493 One and Two-Level Robotic MIS TLIF With Expandable Implants Demonstrates a Favorable Safety Profile and Improved Alignment Parameters
Authors: Moskalik Anzhela D. , Castillo Jose Antonio , Soufi Khadija , Perez Tess , Kercher Matthew , Karnati Tejas , Goodrich Dylan , Kim Kee , Ebinu Julius O. , Martin Allan R.
Published: March 2023

INTRODUCTION:

Minimally invasive surgery (MIS) transforaminal lumbar interbody fusion (TLIF) is an established technique, but continues to evolve with the development of expandable titanium cages and robotic screw insertion.

METHODS:

This retrospective case series assessed clinical data, complications, and radiographic outcomes at short term follow-up. Screw placement was performed using intraoperative 3D imaging and robotic navigation, and TLIFs were performed via complete facetectomy from a unilateral trajectory in line with pedicle screws using titanium expandable cages.

RESULTS:

22 patients, 32 levels, and 108 inserted screws were analyzed. Implants included curved cages in 14 levels, 2 straight cages (diverging “V” pattern) in 12 levels, and a single straight cage in 6 levels. 21/22 patients (95%) had decreased pain. 4/22 patients (18%) experienced complications including deep infection causing screw pullout (requiring revision), painful radiculopathy, contact dermatitis (glue), and UTI. 108/108 screws (100%) showed excellent position. Increases were observed in average segmental lordosis (4.3 ± 4.9°), anterior disc height (6.6 ± 3.5 mm), posterior disc height (4.1 ± 2.1 mm), and foraminal height (5.0 ± 3.1 mm). Improved alignment was observed in 3/3 patients (100%) with SVA > 50 mm (78.3 ± 13.3 mm to 41.7 ±14.3 mm), 3/4 (75%) with pelvic tilt >=25° (30.3 ± 1.5° to 22.7 ± 4.0°), 5/5 (100%) with lumbopelvic mismatch > 10° (PI – LL: 21.4 ± 2.1° to 9.8 ± 8.5°), 13/13 (100%) with anterolisthesis (6.5 ± 2.3 mm to 1.8 ± 1.9 mm), and 4/4 (100%) with segmental coronal imbalance >5° (8.0 ± 3.2° to 2.8 ± 1.3°).

CONCLUSIONS:

Robotic MIS TLIF with expandable cages has a favorable safety profile, successful short-term clinical results, and is effective at correcting mild spinal malalignment.
496 Erector Spine Plane Block Improves Analgesia After Minimally Invasive Awake Spine Surgery
Authors: De Biase Gaetano , Colontonio Matthew , Quinones-Hinojosa Alfredo , Abode-Iyamah Kingsley O. , Bojaxhi Elird
Published: March 2023

INTRODUCTION:

There is an emerging interest in lumbar spine surgery under spinal anesthesia (SA). Bilateral lumbar erector spinae plane (ESP) blocks are also described as a useful regional anesthetic technique to reduce post-operative pain after lumbar surgery.

METHODS:

A retrospective chart review was performed analyzing time in OR, first pain score in PACU after spinal wore off, pain scores throughout POD0, opioid requirements, PONV requiring rescue agent, and length of stay in patients that underwent spine surgery under SA before our practice adopted ESP blocks for back surgery versus patients that received an ESP block. For patients that received an ESP block, the injection was performed after skin closure above the level of the surgical intervention. Under ultrasound guidance, the erector spinae muscle layer was visualized and the block was performed with 15 ml of 0.5% bupivacaine mixed with 15 ml of liposomal bupivacaine (30 ml of local anesthetic per side).

RESULTS:

There was no significant difference in age, sex, ASA class, and BMI. Perioperative opioid use on POD0 was more than double in those not receiving a block (p = 0.0032). First pain score in recovery following conclusion of the spinal was greater than those who had received the intervention, p = 0.0209. Median length of stay in days was the same with a larger range in the non-intervention group. Incidence of nausea/vomiting was decreased in the group receiving ESP blocks.

CONCLUSIONS:

An ESP block can be used as an adjunct for minimally invasive spine surgery for enhancing recovery. Preliminary data suggests there is a trend for lower incidence of PONV as well as average pain scores on POD0 and a significant decrease in perioperative opioid use, increased same-day discharges, and improved pain scores upon conclusion of SA.
498 Feasibility and Efficacy of Postoperative Diffusion Basis Spectrum Imaging to Evaluate Recovery After Surgery in Cervical Spondylotic Myelopathy
Authors: Zhang Justin , Javeed Saad , Greenberg Jacob K. , Dibble Christopher , Jayasekera Dinal , Blum Jacob , Song Sheng-Kwei , Ray Wilson Zachary
Published: March 2023

INTRODUCTION:

Previous studies evaluating diffusion tensor imaging (DTI) in cervical spondylotic myelopathy (CSM) have demonstrated limitations in assessing postoperative outcomes following surgery. Diffusion basis spectrum imaging (DBSI), capable of providing granular assessments of spinal cord microstructure, may help address these shortcomings.

METHODS:

Twenty-seven CSM patients underwent preoperative diffusion-weighted MRI followed by cervical decompressive surgery and repeat imaging at two-years follow-up. DTI and DBSI metrics were extracted from the C3 spinal cord level. Diffusion-weighted MRI anisotropic tensors evaluated white matter tracts through fractional anisotropy, axial diffusivity, radial diffusivity, and fiber fraction. DBSI isotropic tensors assessed extra-axonal pathology through restricted and non-restricted fraction. Improvement after surgery was defined as a 2-point increase in the mJOA at two-years follow-up. Support vector machine classification algorithms were used to predict surgical outcomes.

RESULTS:

Fifteen mild (mJOA 15-17), 7 moderate (12-14) and 5 severe (0-11) CSM patients underwent surgical decompression and were followed-up to 23.2 (5.6, range 11.1-32.8) months postoperatively. Among DBSI metrics, isotropic diffusion components changed significantly from baseline to latest follow-up (p < 0.01), whereas anisotropic components remained stable (p > 0.05). When predicting improvement in the mJOA, SVM models built with DTI metrics had an accuracy of 74.1 [95% CI: 73.6, 74.6] compared to 85.2 [84.5, 85.3] in the DBSI model.

CONCLUSIONS:

Postoperative DBSI metrics predicted long-term outcomes with high accuracy. DBSI may have utility in assessing recovery trajectories for CSM patients following surgery.
501 Patient-Specific Targeting Method for Improved Quality-of-Life Outcomes from MRgFUS Treatment of Essential Tremor
Authors: Datta Anjali , Loo Kung Gustavo Chau , Barbosa Daniel , Quah Kristen , Purger David Arnold , Ren Alexander , Wang Allan , Chodakiewitz Yosefi , Tov Lior Lev , Ghanouni Pejman , McNab Jennifer , Buch Vivek
Published: March 2023

INTRODUCTION:

MRI-guided-focused-ultrasound (MRgFUS) ablation of the ventral intermediate nucleus (VIM) is an FDA-approved treatment for essential tremor (ET). However, the VIM cannot be directly visualized on standard imaging, and the ideal ablation zone within the putative VIM varies inter-individually. Suboptimal lesion location can lead to side effects that impair quality of life (QoL). Patient-specific methods to locate the “go-zone” for MRgFUS ablation for ET that can predict QoL outcome could provide significant benefit over current methods.

METHODS:

We retrospectively studied 26 ET patients treated with MRgFUS at Stanford. Probabilistic tracking from the thalamus to M1 using each subject’s standard, low-resolution preoperative diffusion MRI generated patient-specific cerebello-thalamic-cortical tracts. Within the thalamus, the personalized hotspot with high probability of being connected to M1 defined the “go-zone.” The normative DISTAL-atlas VIM, which some centers use to target deep brain stimulation, provided a comparison. The lesion was segmented in postoperative MRIs and transformed to the preoperative-MRI space. Similarity/overlap between the “go-zone” and lesion was quantified using the Sorensen-Dice coefficient. Postoperative QoL ("better," "same," or "worse") was determined from each subject’s last-available follow-up.

RESULTS:

Probabilistic thalamus-to-M1 tracking robustly identified cerebello-thalamo-cortical tracts using standard, clinical diffusion MRIs. Lesion similarity to the patient-specific tractographic "go-zone" was associated with better QoL outcomes. Dice coefficients of the "worse" group were significantly lower than of the combined “same”/”better” group (p = 0.014). This was not seen with the DISTAL-atlas VIM.

CONCLUSIONS:

We proposed a clinically-feasible probabilistic-tractography-based targeting method for MRgFUS treatment of ET. Lesion similarity to the personalized “go-zone” is associated with better QoL outcome, unlike similarity to the normative DISTAL-atlas VIM. This illustrates the value of our patient-specific targeting approach.
502 Clinical Outcomes for Treatment of Peri-Rolandic Epilepsy
Authors: Lee Anthony T. , Spiedel Benjamin , Knowlton Robert C. , Rao Vikram , Chang Edward
Published: March 2023

INTRODUCTION:

Treatment of epileptogenic foci within the eloquent peri-Rolandic region (pre- and post-central gyri) is challenging. Advances in surgical techniques and implantable neuromodulation devices have broadened the available treatment options.

METHODS:

We retrospectively studied all consecutive patients who underwent intracranial seizure monitoring from 2013 to 2021. We studied demographic and imaging variables, stimulation results, seizure outcomes, and neurological function at various stages of recovery.

RESULTS:

22 patients encompassing 25 procedures were included in this study. 12 of the patients had non-lesional MRIs with surgical intervention involving the dominant hemisphere. 9 patients underwent peri-Rolandic resections, and 11 patients received peri-Rolandic RNS. The rest had a combination of non-peri-Rolandic resection, multiple subpial transection, and peri-Rolandic RNS. When comparing resection against RNS cohorts, more patients who elected for resection had failed prior surgical interventions. Although most resection patients had a neurological deficit at discharge (78% for resection vs 0% for RNS), those who received resection had better rates of seizure control (Engel I at last follow-up: 78% for resection vs 27% for RNS). Almost all patients with neurological deficits experienced significant functional recovery over time.

CONCLUSIONS:

Resection of peri-Rolandic seizure foci can lead to excellent outcomes with neurological morbidity that improves over time. Treatment selection should be tailored based on risk-benefit analysis and patient preference.
507 Apathy Following Bilateral Subthalamic Deep Brain Stimulation for Parkinson’s Disease: The INTREPID Randomized Controlled Trial
Authors: Stiep Tamara , Ramirez-Zamora Adolfo , Tröster Alexander , Jain Roshini , Chen Lilly , Malekmohammadi Mahsa , Okun Michael S.
Published: March 2023

INTRODUCTION:

Motivational disturbances including apathy have been reported following bilateral subthalamic deep brain stimulation (STN-DBS). Many studies suggest apathy is associated with dopaminergic denervation and can be unmasked by drug withdrawal and by aggressive drug tapering following surgery. Additionally, it is suspected that stimulation of the limbic-associative sub-regions of STN might serve as a catalyst, an independent cause, or possibly act synergistically with dopaminergic medication reduction.

METHODS:

INTREPID (NCT01839396) is a multi-center, prospective, double-blinded RCT. Participants with advanced Parkinson's disease (PD) received bilateral STN-DBS and completed a neuropsychological battery at screening (prior to DBS) and at follow up (12-months). Apathy was assessed using the Starkstein Apathy Scale (SAS). Demographic and clinical data including age, gender, disease duration, levodopa-equivalent daily dose (LEDD), and imaging correlates of DBS (including location and volume of stimulated tissue) were analyzed.

RESULTS:

There were a total of 160 subjects evaluated at 1-year following STN-DBS, 44 (27.5%) reported an improvement in apathy scores of at least 5-points, and 7 (4.4%) an improvement >10 points. Eighteen (11.3%) participants had worsening apathy scores >5 points, and 8 (5%) reported worsening >10 points. Aggregation of stimulation field models (SFM) across the cohorts, indicated that worsening of apathy was associated with activation of limbic and associative areas of the STN.

CONCLUSIONS:

Bilateral STN-DBS in this prospective dataset revealed both improvement and worsening of apathy at 1-year follow-up visits. Further analysis of LEDD, dopamine agonist use, and volume of tissue activation may help us to understand the clinical factors underpinning apathy following DBS. Appropriate counseling preoperatively coupled with post-operative monitoring is important for setting expectations and for employing appropriate treatment when necessary.
512 Mapping High Gamma Neural Signals in Hand Primary Somatosensory Cortex Using a Multi-Thousand Channel Platinum Nanorod Microelectrode Grid
Authors: Shahin Maryam Nour , Ramos Christian Lopez , Tchoe Youngbin , Nerison Caleb , Lee Jihwan , Lee Keundong , Bourhis Andrew , Dayeh Shadi , Raslan Ahmed M.T. , Collins Kelly
Published: March 2023

INTRODUCTION:

Neurological deficits secondary to pathologies such as stroke, tumor, trauma, and neurodegeneration lead to enduring disability for many patients. Therefore, the development of neurorestorative technologies utilizing brain computer interfaces (BCIs) is an important goal in applied neuroscience. The high-gamma electrocorticographic (ECoG) neural signals from surgically implanted brain electrodes can be used as an indirect proxy for neuronal spiking activity and local neuronal output, which has translated into an effective control signal for BCIs. Direct electrical stimulation (DES) of primary somatosensory cortex has been used to provide sensory feedback in bi-directional sensorimotor BCIs (BBCIs).

METHODS:

During an awake craniotomy for tumor resection, a PtNRGrid was placed over primary hand somatosensory cortex while touches were applied to the ipsilateral and contralateral hand and arm.

RESULTS:

Here, we demonstrate the mapping of the high gamma signal in single digit and individual carpal distribution.

CONCLUSIONS:

This is the first analysis of high gamma signal in human hand primary somatosensory cortex utilizing PtNRGrids.
513 Presurgical Identification of Seizure Onset and Propagative Zones Without Ictal Recordings: A Combined Diffusion MRI and SEEG Study
Authors: Johnson Graham Walter , Doss Derek , Shless Jared , Paulo Danika Lea , Morgan Victoria , Bick Sarah K.B. , Englot Dario J.
Published: March 2023

INTRODUCTION:

Increasing evidence has suggested that identification of regions involved in early seizure propagation (“Propagation Zones”, PZ) is important to predict seizure freedom after epilepsy surgery (Andrews 2019). Resting-state connectivity analyses using stereo-electroencephalography (SEEG) have shown promise in efficiently characterizing seizure onset zones (SOZ) but have found difficulty in distinguishing both SOZs and PZs from non-involved brain regions. Recently, evidence has suggested that ictal structure-function coupling can be used to delineate brain regions important in seizure dynamics (Shah 2019).

METHODS:

We calculated the resting-state SEEG directed connectivity of 26 consented patients with focal epilepsy undergoing presurgical evaluation. Using preoperative diffusion MRI, we then implemented a custom technique to obtain structural connectivity metrics between SEEG contacts. We calculated the structural connectivity and structure-function coupling of SOZs, PZs (spread within 10 seconds), and non-involved regions over a range of Euclidean distances. Finally, we generated models using a support vector machine to classify SOZs, PZs, and non-involved regions.

RESULTS:

SOZs and PZs exhibit comparably high local structural connectivity compared to non-involved regions despite SOZs demonstrating significantly greater functional connectivity to both PZs and non-involved regions. However, PZs exhibit significantly higher local structure-function coupling to that of non-involved regions, with SOZs exhibiting the highest local structure-function coupling. A support vector machine to classify SOZs, PZs, and non-involved regions and was able to significantly increase model accuracy by incorporating local structure-function coupling.

CONCLUSIONS:

SOZs and PZs demonstrate a distinct local structure-function coupling to that of non-involved regions and each other. This distinct coupling profile can be used to accurately classify SOZs, PZs and non-involved regions.
514 A Functional Ultrasound Brain-Machine Interface: Real-Time Decoding of Eight Movement Directions
Authors: Griggs Whitney , Norman Sumner , Rabut Claire , Deffieux Thomas , Christopoulos Vasileios , Liu Charles Y. , Tanter Mickael , Shapiro Mikhail , Andersen Richard
Published: March 2023

INTRODUCTION:

Brain-machine interfaces (BMIs) can be transformative for people living with chronic paralysis. By translating brain signals into computer commands, BMIs can bypass neurological impairments, enabling users to control computers, robots, and more. State-of-the-art BMIs have already made this future a reality in limited clinical trials. However, these BMIs requires inserting highly invasive electrodes into the brain. Device degradation limits longevity to 3-5 years and the field of view of brain activity is small. These factors limit BMI’s widespread adoption. The next generation of BMIs must be longer lasting, less invasive, and scalable. Functional ultrasound neuroimaging (fUSI) is a recently developed technique that meets these criteria.

METHODS:

We collected data from two nonhuman primates (NHPs). We used real-time fUSI to measure activity in the posterior parietal cortex, an important area for motor planning. We fed this fUSI data into real-time machine learning classifiers to predict the monkey’s intended movement direction and control a behavioral task in real-time.

RESULTS:

We could predict the monkey’s intended movement direction significantly above chance level (binomial test, p<0.001 for 2- and 8-directions) using the real-time fUSI-BMI. Most direction misclassifications were for neighboring directions (permutation test, p<0.001). The most important voxels for decoding eye movements were within small subpopulations of the lateral intraparietal area (LIP). We found that these LIP subpopulations had a stable encoding of movement direction and the NHPs could accurately control the task more than 40 days after training the decoder model.

CONCLUSIONS:

This work establishes, for the first time, the feasibility of a real-time ultrasound-based BMI and we have begun translating this work into human applications. This work contributes to the next generation of high-performing, yet minimally-invasive, BMIs that can restore function to patients with neurological impairments.
517 Glioblastoma Induces the Recruitment of Anti-Tumoral Immunostimulatory Neutrophils from Skull Bone Marrow
Authors: Lad Meeki , Beniwal Angad , Gill Sabraj , Jain Saket , Aghi Manish Kumar
Published: March 2023

INTRODUCTION:

The effects of tumor-associated neutrophils (TANs) on glioblastoma biology remain poorly understood. While TANs are generally considered immunosuppressive, recent studies have demonstrated their ability to present antigen to T cells, warranting investigation of this phenotype in glioblastoma.

METHODS:

Flow cytometry was used to sort and characterize surface protein expression among neutrophils across 5 newly diagnosed glioblastoma fresh tissue specimens. Samples were evaluated transcriptomically via single-cell RNA sequencing (scRNA-seq) or phenotypically via coculture with autologous T cells. TANs were further evaluated in a syngeneic glioma mouse model (Balb/c), treated with either neutrophil-depleting antibody (αLy6G) or isotype control; tumor size was ascertained by bioluminescent imaging. Skull bone marrow was tagged with fluorescent dye in neutrophil tracing experiments.

RESULTS:

21.0-34.1% of patient glioblastoma TANs express MHCII, a marker of antigen-presenting cells not canonically associated with neutrophils and not expressed in matched peripheral blood (PBNs). scRNA-seq pseudotime analysis demonstrates that antigen-presenting neutrophils are a developmental lineage seen uniquely in TANs and not PBNs, with enriched expression of MHCII subunits (HLA-DR), chaperones (HLA-DM), and costimulatory ligands (CD86/83;). Consequently, TANs activate T cells in an MHCII-dependent manner (CD25 MFI fold-change, PBNs vs TANs: 1.1 vs 3.2, p < 0.001), and depleting neutrophils in a murine model yields endpoint tumors that have 53% lower CD8+ T cell infiltration (n = 13, p = 0.0024) and are 2.4-fold larger (p = 0.0383). The lack of MHCII+ neutrophils in blood suggests that these cells may be recruited from local marrow niches and not circulation; indeed, in vivo, we observe that compared to all TANs, MHCII+ TANs are disproportionately derived from skull bone marrow (41.7% vs 9.3%).

CONCLUSIONS:

Given the recruitment of immunostimulatory TANs from the calvarium to the glioblastoma microenvironment, mechanisms to enhance neutrophil transmarrow migration may have therapeutic value.
519 Single Nucleus ATAC Sequencing Reveals Increased PPP1R17 Chromatin Accessibility Driving Cushing’s Disease
Authors: Asuzu David , Stoica Stefan , Elkahloun Abdel , Johnson Kory , Chittiboina Prashant
Published: March 2023

INTRODUCTION:

Epigenetic drivers of pituitary adenomas causing Cushing’s disease (CD) are virtually unknown. Here, we investigate the epigenetic mechanisms underlying gene dysregulation in CD.

METHODS:

We isolated single nuclei from 3 CD adenoma – normal gland pairs and performed single nucleus RNA sequencing (snRNAseq) and assays for transposase-accessible chromatin (snATACseq, 10x Genomics). We integrated these data with prior paired single cell data (scRNAseq, n = 3) and bulk RNAseq (CD = 3, non-CD = 3). We performed bulk DNA methylation assays on independent adenomas (CD = 3, non-CD = 3; Illumina Infinium MethylationEPIC). CD adenomas were examined by multiplexed immunohistochemistry (mIHC). We generated murine corticotroph (mCort) cell lines stably transfected with lentiviral expression vectors (Origene) and assessed for cell-cycle changes (Click-IT EdU) and cell proliferation (OneGlo).

RESULTS:

snATACseq and snRNAseq data identified increased chromatin accessibility with upregulated PPP1R17 expression in single nuclei from CD adenomas, in agreement with our prior scRNAseq and bulk RNAseq data (16-fold in paired analysis, FDR < 0.01). DNA methylation failed to identify global or local differential methylation at the PPP1R17 locus. mIHC confirmed PPP1R17 protein overexpression in human CD tumors. PPP1R17 overexpression in mCort cells accelerated the cell cycle with fewer cells accumulating in S-phase (16.4% vs 24.1%, P < 0.01), and increased cell proliferation (two-way ANOVA P < 0.01).

CONCLUSIONS:

We identified coordinated chromatin accessibility, transcriptional activation and protein expression of PPP1R17 in human CD adenomas compared to surrounding normal tissues, and recapitulated hyperproliferation in-vitro by stable PPP1R17 overexpression. Our findings uncover targetable epigenetic mechanisms in CD pathogenesis.
520 Glioblastoma Susceptibility to SARS-CoV-2: Analysis of Cancer Stem Cells and Immune Tumor Microenvironment on Human Brain, Patient-Derived Tumors, and Organoid Models
Authors: Ruiz Garcia Henry Jeison , Watanabe Fumihiro , Suarez-Meade Paola , Rafferty Seamus , Garcia Diogo P. , Jentoft Mark E. , Schiapparelli Paula , Imitola Jaime , Quinones-Hinojosa Alfredo
Published: March 2023

INTRODUCTION:

Glioblastoma (GBM) is the most common and deadliest primary brain tumor, characterized by chemoradiation resistance and an immunosuppressive tumor microenvironment (TME). SARS-CoV-2, the COVID-19 virus, produces a significant pro-inflammatory response and a spectrum of clinical presentations after central nervous system infection.

METHODS:

Patient-derived GBM tissue, primary cell lines, and organoids were analyzed with immunohistochemistry and pixel-line intensity quantification. Data from tumor-bulk and single-cell transcriptomics served to describe the cell-specific expression of SARS-CoV-2 receptors in GBM and its association with the immune TME phenotype. Normal brain and iPSC-derived organoids served as controls.

RESULTS:

We demonstrate that patient-derived GBM tissue and cell cultures express SARS-CoV2 entry factors such as ACE2, TMPRSS2, and NRP1. NRP1 expression was higher in GBM than in normal brains (p<0.05), where it plays a crucial role in SARS-CoV-2 infection. NRP1 was expressed in a cell-type and phenotype-specific manner and correlated with TME infiltration of immunosuppressive cells: M2 macrophages (r = 0.229), regulatory T cells (r = 0.459), NK cells (r = -0.346), and endothelial cells (r = 0.288) (p < 0.05). Furthermore, gene ontology enrichment analysis showed that leukocyte migration and chemotaxis are among the top 5 biological functions mediated by NRP1 (p < 0.05). We found our GBM organoids recapitulate tumoral expression of SARS-CoV-2 entry factors, which varies based on distance from surface as surrogate of TME oxygenation (p < 0.05).

CONCLUSIONS:

GBM cancer cells and immune TME cells express SARS-CoV-2 entry factors. Glioblastoma organoids recapitulate this expression and allow for currently undergoing studies analyzing the effect of SARS-CoV-2 infection in GBM. Our findings suggest that SARS-CoV-2 could potentially target GBM, opening the door to future studies evaluating SARS-CoV-2-driven immune modulation.
522 Metabolomic Analysis of 54 Meningiomas Reveals Distinct Metabolite Profiles in WHO 1 and WHO 2/3 Tumors
Authors: Dougherty Mark Chrysostom , Taylor Eric , Hansen Marlan
Published: March 2023

INTRODUCTION:

Meningiomas are the most common primary CNS tumor. Yet when surgical and radiation fail, no further treatments exist. Metabolomics is the study of metabolic networks and has been used to discover new treatments in cancers; however, few attempts have been made to apply metabolomics to meningiomas.

METHODS:

Primary tumors were obtained from surgeries at the University of Iowa. Primary tumor specimens were immediately flash-frozen in liquid nitrogen, while tissue for culture was placed on ice and immediately transferred for cell culturing. Upon reaching >90% confluence, cultures were treated with 0gy, 3gy, 10gy, or 20gy gamma radiation. Six or 72 hours after radiation the cultures were washed then flash frozen in liquid nitrogen. Metabolomic profiles were obtained with a ThermoISQ gas chromatography-mass spectrometer. Data was analyzed using MetaboAnalyst 5.0.

RESULTS:

Forty WHO grade 1 and fourteen WHO grade 2/3 tumors were included. Eleven tumors were also successfully cultured. Partial least squares-discriminant analysis (PLS-DA) demonstrated expected clustering of primary tumors according to pathologic grade. Among the primary tumors, 12 metabolites were found to be significantly elevated in WHO grade 2/3 tumors.In parallel, primary cell cultures were developed to test the effect of radiation on the tumors, but unsupervised clustering found that inter-tumor heterogeneity was greater than the treatment effect from radiation.

CONCLUSIONS:

High-grade meningiomas display distinct metabolite levels compared to benign meningiomas, suggestive of altered metabolic pathway utilization. Standard cell cultures did not reveal significant metabolic changes following radiation, but it is unclear whether this was due to technique or a true finding. Further experiments are needed to elucidate the functional implications of these findings.
526 Clinical Characteristics and Biomarkers of Aggressive Nonfunctional Pituitary Adenomas and Pituitary Carcinomas
Authors: Aum Diane J. , Hwang Jenie , Rovira Miguel Hernandez , Martirossian Alexandra , Blount Sidney , Silverstein Julie , Kim Albert H.
Published: March 2023

INTRODUCTION:

Nonfunctioning pituitary adenomas (NFPAs) are benign tumors of the pituitary gland. While surgery is the treatment of choice, a subset of aggressive NFPAs is associated with multiple recurrences and treatments. Pituitary carcinomas are a rare group of pituitary tumors, comprised of both functional and non-functional, which metastasize to other locations.

METHODS:

A retrospective review of 601 consecutive patients who underwent endoscopic transsphenoidal surgery between 2010 and 2018 at one institution was conducted. Among 209 NFPA patients, 29 patients had aggressive NFPAs, with ≥2 recurrences and ≥3 treatments. We used Infinium HumanMethylation450 BeadChip arrays along with R (R Core 2014) and Bioconductor for methylation analysis of patients with indolent NFPAs (n = 6), aggressive NFPAs (n = 8), pituitary carcinomas (n = 9), and normal pituitary glands (n=3).

RESULTS:

In multivariate analysis of clinical features, tumor volume and proliferative index were higher in aggressive NFPAs compared to indolent NFPAs. Although significantly different, these features were not specific to aggressive NFPAs. Methylation analysis showed no significant global methylation differences among all samples. However, we identified significant probe-wise differentiation in methylation of over 100 genes between indolent and aggressive NFPA groups. Heat map representation of the most significant differentially methylated genes demonstrated similarity in methylation patterns between the aggressive NFPA and pituitary carcinoma group, which were distinct from the indolent group.

CONCLUSIONS:

Tumor volume and proliferative index were significantly increased in the aggressive compared to the indolent group. In DNA methylation analyses, we identified numerous hypermethylated genes in the aggressive and pituitary carcinoma groups, which were distinct from the indolent group. DNA methylation may provide a useful predictive biomarker to identify aggressive NFPA types and potentially reveal common mechanistic links between aggressive NFPAs and pituitary carcinomas.
528 Robotic Image-Guided LINAC Radiosurgery for Trigeminal Neuralgia: Results After 10 Years
Authors: Romanelli Pantaleo , Thomas Evan M.
Published: March 2023

INTRODUCTION:

Frameless image-guided robotic radiosurgery delivering 60 Gy to a 6mm mid-cisternal/retrogasserian segment of the affected trigeminal nerve was used to treat 702 patients affected by severe Trigeminal Neuralgia(TN) refractory to medications . Clinical outcomes in 92 patients with minimum follow-up of 10 years are here reported.

METHODS:

702 patients with severe, long-standing TN refractory to medications have been treated at the Cyberknife Center of CDI,Milan,Italy over the last 13 years. A dedicated protocol for imaging ( head CT with and without contrast, slice thickness 0,5 mm; brain MR including MPRAGE and CISS/FIESTA sequences) and treatment( selecting a 6 mm segment of the nerve going from the midcisternal toward the retrogasserian region with a dose prescription of 60Gy @80% isodose) was employed. Regular clinical follow-up was performed one or more times per year according to clinical needs and distance from the treatment. Recurrent pain was treated with the same protocol( a lower dose of 45 Gy was later selected for retreatments).

RESULTS:

Pain control rates of 92%,87%,76%,74% after respectively 1,2, 3 and 5 years have been found. 92 patients with follow-up longer than 10 years show pain control rate of 72% while the rate of persistent bothering parethesias is 5, 4% (5 patients). No other neurological complications have been found.

CONCLUSIONS:

Long-term follow-up shows that frameless Linac radiosurgery provides long-term pain control in over 2/3 of the treated patients, with low rate of sensory complications and no other neurological complications.
529 Neuro-Oncology Practice Patterns and Management Paradigms: A Global Epidemiological Survey
Authors: Haizel-Cobbina Joseline , Chotai Silky , Labuschagne Jason , Belete Addisalem , Sichizya Kachinga , Ahmad Misbahu Haruma , Nketiah Boakye Frank , Shabani Hamisi , Dewan Michael C.
Published: March 2023

INTRODUCTION:

Understanding of the epidemiology and biology of pediatric central nervous system (CNS) tumors has advanced dramatically over the last decade; however there remains a discrepancy in the understanding of epidemiologic and clinical capacity-oriented data between high income and low middle- or low-income countries.

METHODS:

A cross sectional epidemiological survey was conducted to determine the incidence, diagnosis, management, and follow-up paradigm for pediatric CNS tumors using REDCap. The survey was administered to neurosurgeons at partner hospitals, collecting aggregate data for patients managed over the preceding 3-months. The survey was sent to the sites 3 times at 3-months interval. Descriptive statistics analyses were performed.

RESULTS:

Fourteen percent of outpatient and 13% of operative volume was represented by pediatric neuro-oncology at the partner sites. Only one site had no diagnostic modality available at, others had either CT scan only or both CT scan and MRI. Of 214 patients evaluated, 128 (59.8%) underwent surgery and 16 (7.5%) were referred to other centers. Mean 29.2% patients did not undergo surgery due to inadequate resources. Mean 44.4% received adjuvant chemotherapy and 27.6% received adjuvant radiotherapy when indicated. The most common tumor location was posterior fossa (26.7%). The most common pathology diagnosis was low grade glioma (17.4%). None of the six partner sites had neuropathology expertise.

CONCLUSIONS:

A wide variety of pediatric brain and spine tumor pathology was managed at these six national referral sites in Sub-Saharan African countries. The histopathological profile of the tumors managed at these sites was akin to previously published studies. Further resource allocation focusing on setting up pediatric neuro-neuro-oncology practices might improve care for these patients.
550 Hospital Frailty Risk Score is an Independent Risk Factor for VP Shunt Placement for Ruptured Intracranial Aneurysms
Authors: Koo Andrew B. , Elsamadicy Aladine A. , Sarkozy Margot , Reeves Benjamin , Craft Samuel , Sherman Josiah , Sayeed Sumaiya , Antonios Joseph Paul , Renedo Daniela , Sujijantarat Nanthiya , Hebert Ryan Matthew , Malhotra Ajay , Matouk Charles Christian
Published: March 2023

INTRODUCTION:

Frailty is an important predictor of poor surgical outcomes. Identifying patients who will require ventriculoperitoneal (VP) shunt placement following endovascular management for ruptured intracranial aneurysms (IA) remains poorly understood.

METHODS:

A retrospective study of the National Inpatient Sample database (2016-2019) was performed. Patients ≥18 years old undergoing endovascular treatment for IA after subarachnoid hemorrhage identified using ICD-10-CM coding were dichotomized by whether they underwent VP shunt placement during the index admission. Only patients with coding for initial external ventricular drain placement were included. Demographics, comorbidities, adverse events (AEs), LOS, discharge disposition and total cost were assessed. A multivariate analysis was used to assess the influence of HFRS on VP shunt placement.

RESULTS:

Of the 12,935 patients identified, 2,805 (21.7%) required VP shunt placement. The shunt population was older (No Shunt: 56.6 ± 13.5 years vs. Shunt: 58.5 ± 12.6 years, p = 0.002). HFRS-defined frailty was greater in the shunted population (No Shunt: 11.1±5.4 vs Shunt: 12.3 ± 5.5, p<0.001). The shunted population experienced more AEs (No Shunt: 83.2% vs. Shunt: 89.5%, p < 0.001). Mean LOS (No Shunt: 23.0 ± 13.6 days vs Shunt: 31.7 ± 18.9 days, p<0.001), mean cost (No Shunt: $115,808 ±64,428 vs Shunt: $160,024 ± 92,014, p < 0.001), and non-routine discharge (No Shunt: 64.5% vs Shunt: 79.9%, p < 0.001) were greater in patients shunted. On multivariate analysis, several risk-factors were associated with VP shunt placement, including frailty, age, female sex, hydrocephalus, dysphagia, pulmonary circulation disorders, other neurological disorders, and aneurysm location. The odds ratio for Frailty was 1.53 (p = 0.025) for intermediate-frailty patients and 1.69 (p=0.011) for high-frailty patients compared to low-frailty patients.

CONCLUSIONS:

Our study demonstrates that HFRS is an independent predictor of VP shunt placement following endovascular treatment of ruptured intracranial aneurysms.
553 Mechanical Thrombectomy for the Treatment of Anterior Cerebral Artery Occlusion
Authors: Dabhi Nisha , Mastorakos Panagiotis , Sokolowski Jennifer D. , Kellogg Ryan Thomson , Park Min S.
Published: March 2023

INTRODUCTION:

Strokes of the anterior cerebral artery (ACA) and its branches account for up to 4.4% of ischemic strokes and have been associated with disability after discharge. While mechanical thrombectomy (MT) has been established to be safe and highly effective in the treatment of thromboembolic occlusion of the middle cerebral artery, internal carotid artery, and basilar artery, to date, the safety and efficiency of MT for the treatment of acute ACA occlusions have not been clearly delineated.

METHODS:

A systematic literature review was performed for outcomes data in patients with MT-treated ACA occlusions using Pubmed, Ovid Medline, and Web of Science. Recanalization, procedural data, and clinical outcome at last follow-up were collected and summarized.

RESULTS:

In the nine included studies, there were 196 patients with ACA strokes treated with MT, of which 65% (109/168), 34% (57/168), and 33% (56/168) had primary isolated ACA occlusion, primary combined ACA occlusion, and secondary ACA occlusion, respectively. Recanalization mTICI2b/3 was achieved in 80% (134/168), and procedural complications occurred in 23% (39/168) of patients. At the three-month follow-up, mortality rate was 19% (20/106) and rate of good functional outcome was 32% (48/148).

CONCLUSIONS:

MT for the treatment of ACA occlusions is a relatively safe and efficacious option, offering a favorable rate of recanalization and procedural complications. However, MT-treated ACA occlusions are associated with a lower rate of short-term good functional outcome. More single and multicenter studies are needed to further examine the safety and efficacy of MT in ACA occlusions.
555 A Shift from Open to Endovascular Repair in the Treatment of Ruptured Middle Cerebral Artery Aneurysms and its Association With Improved 6-Month Functional Outcomes: A Single Institution Experience
Authors: Diestro Jose Danilo , Li Yangmei , Omar Buddy , Kishore Kislay , Montanera Walter , Sarma Dipanka , Marotta Thomas , Spears Julian , Baratha Aditya
Published: March 2023

INTRODUCTION:

Middle cerebral aneurysms were underrepresented in the two largest trials (BRAT and ISAT) for the treatment of ruptured intracranial aneurysms. Recent institutional series addressing the choice between endovascular or open repair for this subset of aneurysms are few and have not yielded a definitive conclusion.

METHODS:

We conducted a retrospective review of 138 consecutive patients with ruptured middle cerebral artery aneurysms admitted into our institution from March 2009 to March 2019 to compare endovascular and open surgical outcomes.

RESULTS:

Of the ruptured middle cerebral artery aneurysms, 57 underwent endovascular repair while 81 were treated with open surgery. Over the study period there was a notable shift in practice toward more frequent endovascular treatment of ruptured MCA aneurysms (31% in 2008 vs. 91% in 2018). At discharge (49.1% vs 29.6%; p = .002) and at 6 months (84.3% vs 58.6%; p = 0.003), patients who underwent endovascular repair had a higher proportion of patients with good clinical outcomes (mRS 0-2) compared to those undergoing open surgery. Long term follow-up data (endovascular: 54.9 ± 37.9 months vs clipping: 18.6 ± 13.4 months) showed rebleeding (1.8% vs 3.7%, p = 0.642) and retreatment (5.3% vs 3.7%, p=0.691) in both groups.

CONCLUSIONS:

Our data suggest that endovascular repair was a feasible treatment strategy associated with improved functional outcome at 6 months. Future randomized trials for MCA aneurysms could further clarify the roles of these treatment modalities.