bluuebunny/crossref_metadata_2025 huggingface dataset:
1228 Comprehensive T-cell Profiling in Chordomas: Single-cell RNA-Seq and TCR Profiling Analysis Uncover Antitumor and Exhaustion Phenotypes for Targeted Immunotherapies
Authors: Arrieta Victor Andrés , Benotmane Jasim K. , Zhao Junfei , Dhiantravan Silpol , Hou David , Katz Joshua L. , Wang Si , Castro Brandyn , Pandey Surya , Cholak Meghan E. , Han Yu , Bettegowda Chetan , Horbinski Craig , Miska Jason , Stupp Roger , Lesniak Maciej S. , Sonabend Adam M. , Wolinsky Jean-Paul , Heiland Henrik , Chang Catalina Lee
Published: March 2024

INTRODUCTION:

Chordomas, a rare type of tumor, originate from residual notochord tissue. These tumors present important challenges due to the limited treatment options. Investigating the intricacies of T-cell composition and function in chordoma immunity holds the potential to advance immunotherapy strategies for these patients.

METHODS:

We generated a comprehensive single-cell atlas of T cells of chordomas, incorporating paired single-cell transcriptomic samples from the tumor and blood of five patients and single-cell TCR sequencing data to assess T-cell clonality. Additionally, we analyzed T cells in 33 chordomas (22 newly diagnosed and 11 recurrent tumors) using multiplex immunofluorescence.

RESULTS:

Our results demonstrate that CD8+ T-cell antitumoral immunity originates in the periphery, marked by clonal expansion of cytotoxic and memory T cells in the blood. However, this immunity experiences progressive exhaustion upon tumor infiltration. Notably, a large percentage of CD8+ T-cells from the tumors and blood shared their TCRs with exhausted CD8+ T-cells known for tumor specificity, confirming the origin of a peripheral antitumor response. We identified specific antigen peptide sequences through TCR analysis that were enriched in exhausted T cell receptors' binding sites that uncovered shared motifs within the reactive tumor-infiltrating compartment. Moreover, we observed that CTLA-expressing central memory and Tregs made up most of the CD4 T-cell tumoral landscape. Interestingly, multiplex immunofluorescence showed a higher abundance of CD3+ T cells in newly diagnosed chordomas compared to recurrent cases.

CONCLUSIONS:

This study sheds light on the composition and function of T cells in chordomas, revealing the origin and exhaustion of CD8+ T-cell antitumor immunity. These findings contribute to our understanding of chordoma immunity to guide the development of targeted immunotherapies for both newly diagnosed and recurrent cases.
1230 Intraventricular Meningioma Resection and Visual Outcomes
Authors: Andrews John P. , Cummins Daniel Dighton , Morshed Ramin , Kinde Benyam , Aghi Manish Kumar , McDermott Michael William , Berger Mitchel S. , Theodosopoulos Philip V.
Published: March 2024

INTRODUCTION:

Intraventricular meningiomas (IVMs) of the lateral ventricle are rare tumors that present surgical challenges due to their location. Visual field deficits (VFDs) are one risk associated with these tumors and their treatment. VFDs may be present preoperatively due to the tumor and mass effect (i.e. tumor-VFDs) or may develop postoperatively due to the surgical approach (surgical-VFDs).

METHODS:

Patients who received IVM resection at one academic institution (1996-2021) were retrospectively reviewed. Diffusor tensor imaging (DTI) reconstructions of the optic radiations around the tumor were performed from preoperative imaging. VFD course and resolution were documented. A systematic review was conducted for studies on surgical resection for IVMs that included >5 patients and reported postoperative neurologic outcomes.

RESULTS:

In the institutional series, thirty-two adult patients underwent IVM resection, with gross total resection in 30 patients (93.8%). Pre-operatively, tumor-VFDs were present in 6 patients, resolving after surgery in 5. Five other patients (without pre-operative VFD) had new persistent surgical-VFDs postoperatively (5/32 patients, 15.6%) that persisted to most recent follow-up. Of the 5 patients in the institutional cohort with persistent surgical-VFD, 4 had trans-temporal and 1 had a trans-parietal approach, and all of these occurred prior to regular use of DTI in preoperative imaging. In the systematic review, 14 studies met inclusion criteria and 12 commented on visual outcomes postoperatively. Median rate of tumor-VFDs improving postoperatively was 50% (range 0 to 100%) and median rate of new postoperative surgical-VFDs was 11% (range 0 to 23%).

CONCLUSIONS:

Half of presenting tumor-VFDs from IVMs improve with surgery. However, new surgical-VFDs are a common neurologic deficit after IVM resection. Preoperative DTI may demonstrate distortion of the optic radiations around the tumor, thus revealing safe operative corridors to prevent surgical-VFDs.
1232 Outpatient Stereotactic Needle Biopsy Is a Cost-effective Strategy for Brain Tumor Patient Decision-making That Enhances Clinical Trial Accrual
Authors: Hartke Joelle Nicole , Furey Charuta Gavankar , Asher Anthony Michael , Nidamanuri Sreecharita , Catapano Joshua , Zavala Baltazar , Sanai Nader
Published: March 2024

INTRODUCTION:

Although neuroradiological techniques have expanded, stereotactic needle biopsy is a simple, ubiquitous,and immediate strategy for established or potential brain tumor patients with atypical clinical and/or radiographic findings.

METHODS:

Outpatient stereotactic needle biopsies performed by a single surgeon from August 2020 through November 2022 were retrospectively reviewed. Electronic medical records were queried for clinical, perioperative, and tumor demographics. Financial records were queried for insurance and payment reports. Descriptive statistics were used to characterize comparisons among collected variables.

RESULTS:

107 consecutive stereotactic needle biopsy procedures were conducted in adult brain tumor patients. All biopsies were performed using a single needle-pass in the outpatient setting, targeting supratentorial lesions in 89.7% of cases. Tissue diagnosis was established in 96% of procedures, with glioma being the most common histology. No intraoperative or perioperative complications occurred. Four patients (3.7%) were admitted overnight due to urinary retention (n = 2) and asymptomatic tract hemorrhage (n = 2), respectively. Insurance approval was sought preoperatively from non-commercial (31.7%) and commercial (68.3%) payors and approved in all cases. Postoperatively, 30.8% of patients received an experimental therapeutic on the basis of tissue analysis.

CONCLUSIONS:

We report the largest experience to date with outpatient stereotactic needle biopsy in newly-diagnosed and recurrent brain tumor patients. Our findings identify this strategy as a cost-effective alternative to advanced imaging that facilitates clinical trial accrual through tissue acquisition.
1235 Using Supervised Machine Learning to Validate a Novel Scoring System for the Prediction of Disease Remission of Functional Adenomas Following Transsphenoidal Resection
Authors: McKevitt Chase , Gabriel Ellie , Hillembrand Lina Marenco , Otamendi-Lopez Andrea , Jeevaratnam Suren , Cavalcante de Almeida Joao Paulo , Samson Susan , Chaichan Kaisorn L.
Published: March 2024

INTRODUCTION:

Functional pituitary adenomas are common primary central nervous system tumors with potent systemic endocrinological effects. Postoperatively, remission rates range from 65-98%.

METHODS:

392 adult patients who underwent primary resection of a functional pituitary adenoma at the three Mayo Clinic between 2006-2022 were retrospectively reviewed. Multivariate logistic regression was performed to identify variables predictive of disease remission. Variables found statistically significant on multivariate analysis were incorporated into our proposed pituitary-SCHEME score. Machine learning models were implemented to compare the accuracy of the pituitary-SCHEME score against the multivariate models. After training (314 patients) and cross-validation of the machine learning models, an independent testing set of 78 patients was performed. SPSS V27 and R4.2.1 were used for statistical analyses.

RESULTS:

261 (66.6%) patients achieved post-operative biochemical remission. On multivariate analysis gross-total resection and Knosp-Grade 0,I,II adenomas were predictive of disease remission following resection, while macroadenomas (adenoma > 10mm), male sex, mammosomatotroph and Mixed Growth-Hormone + Prolactin adenomas were predictive of continued disease. In machine learning models, without Pituitary-SCHEME score, the K-Nearest Neighbors (KNN) model achieved the highest accuracy at 75.6% followed by Naive Bayes model. An increase in model sensitivity was achieved with inclusion of Pituitary-SCHEME score with the Linear-Discriminant-Analysis (LDA) model achieving the highest accuracy at 86.9%, followed by the Classification and Regression Trees (CART) model. The random forest model had the largest AUC-ROC among models with and without pituitary-SCHEME score. Model prediction accuracy (with vs. without pituitary-SCHEME score) were found to be statistically different based on Wilcoxon rank sum testing (p < 0.0001).

CONCLUSIONS:

The novel pituitary-SCHEME score, which incorporates perioperative and endocrinological measures, has promise as a clinical tool to predict patient outcomes following surgical resection of functional adenomas.
1237 The Mutational Landscape of Molecularly Defined Oligodendrogliomas
Authors: Weber-Levine Carly , Rakovec Maureen , Jiang Kelly , Kalluri Anita , Raj Divyaansh , Parker Megan , Materi Joshua , Sepehri Sadra , Ferres Abel , Schreck Karisa C. , Aldecoa Iban , Lucas Calixto-Hope , Redmond Kristin , Holdhoff Matthias , Sair Haris , Brem Henry
Published: March 2024

INTRODUCTION:

Oligodendrogliomas are molecularly defined by IDH1/2 mutation and codeletion of chromosome arms 1p/19q. Prior studies identified capicua transcriptional repressor (CIC), far upstream binding protein (FUBP1), and the promoter region of telomerase reverse transcriptase (TERTp) as commonly mutated in oligodendrogliomas. However, prognostically relevant molecular signatures have yet to be identified.

METHODS:

A retrospective single-center study evaluated adults with pathologically confirmed IDH-mutant and 1p/19q co-deleted oligodendrogliomas that underwent surgery between 2005 and 2021. Genetic data from formalin-fixed, paraffin-embedded specimens were analyzed with the NGS Solid Tumor Panel at the Johns Hopkins Medical Laboratories, which tested over 400 genes. Kaplan-Meier curves and log-rank tests were used to compare progression-free survival (PFS) and overall survival (OS). Chi-squared tests compared clinical characteristics between mutation status in the ten most frequently mutated genes.

RESULTS:

From 277 patients with IDH-mutated, 1p/19q co-deleted oligodendrogliomas, 95 patients with NGS were included. Ten genes had 9 or more patients with a mutation, with CIC and FUBP1 being the most frequently mutated genes (n = 60 and n = 23, respectively). Kaplan-Meier curves showed that most genes were not associated with differences in PFS or OS. CIC conferred a reduction in PFS in patients with a PFS <100 months (p = 0.038), though this significance was lost when including all PFS durations (p = 0.52). While no biomarkers had sufficient statistical power, our analysis showed trends in shortened survival in patients with TP53 (p = 0.01) and PIK3CA (p = 0.03) mutations.

CONCLUSIONS:

Oligodendrogliomas harbor frequent mutations in CIC, FUBP1, and TERTp, but most patients typically have minimal additional alterations. As NGS becomes routine, understanding these mutations may inform therapeutic and prognostic recommendations or the development of novel targeted therapies. Additional molecular assays beyond mutation analysis with NGS may reveal prognostically relevant biologic subgroups of oligodendrogliomas.
1238 Next Generation Sequencing of Gliomas to Identify Predictors of Time to Postoperative Epilepsy
Authors: Nguyen Minh P. , Shukla Poojan , Young Jacob , Lee Anthony T. , Chang Edward
Published: March 2024

INTRODUCTION:

Seizures during the course of disease for patients with diffuse gliomas is common. As genetic characterization of gliomas has improved, how a tumors mutational profile influences the timing of postoperative seizures, and if postoperative seizures relate to survival and tumor progression, is poorly understood.

METHODS:

A retrospective review of consecutive adults from 2017 to 2020 who underwent resection of gliomas with next generation sequencing of tumors at a single institution was performed. Cox proportional hazards regression was performed to identify factors associated with time to postoperative seizures. Seizures within 72 hours of surgery were excluded.

RESULTS:

363 patients with newly diagnosed or recurrent tumor tissue genotyped via next generation sequencing were included. Median follow-up time was 37.4 months, median time to seizure after surgery was 39.2 months (95% CI 34.6 – 60.8), and IDH-mutant tumors comprised 38.3% of the cohort. Patients with IDH-mutant tumors were more likely to have non-immediate postoperative seizures (p = 0.031) and more persistent postoperative seizures (p = 0.004) compared to IDH-wildtype tumors. PDGFRA mutation was associated with shorter time to seizure in IDH-mutant gliomas (p = 0.033), with no such genetic factors in IDH-wildtype tumors. Among IDH-mutant and wildtype tumors, patients with shorter seizure freedom had significantly shorter overall and progression-free survival.

CONCLUSIONS:

PDGFRA mutation is associated with earlier seizures after resection of IDH-mutant diffuse gliomas. Earlier first non-immediate postoperative seizure after resection is associated with worse overall and progression-free survival.
1240 Assessing Survival Outcomes of PCV-Based and Temozolamide-Based Adjuvant Therapy in Oligodendroglioma Patients
Authors: Chen Adrian , Begley Sabrina , Schulder Michael , Goenka Anuj
Published: March 2024

INTRODUCTION:

When treating oligodendroglioma patients, choosing between temozolomide (TMZ) and procarbazine, lomustine, and vincristine (PCV), with concurrent radiotherapy still poses a challenge. Given the commonality of tumor recurrence, optimizing progression-free survival while minimizing adverse effects is crucial to improving quality of life.

METHODS:

87 patients treated for oligodendroglioma between 1994-2022 were retrospectively reviewed. Progression-free survival (PFS) and overall survival (OS) from initial resection were compared between PCV-based or TMZ-based treatment groups using Kaplan-Meier and multi-variable Cox survival analysis.

RESULTS:

The median age at diagnosis was 41 years and 62% were male. After initial resection, 42.8% received PCV-based treatment and 57.2% received TMZ-based treatment. Treatment groups were balanced in the following variables: age, tumor genetic profiling, the extent of resection, and KPS score. However, more patients in the TMZ-based group received concurrent radiation. The entire cohort had a 6.3-year PFS and 21.0-year OS. The median time to recurrence was significantly longer in those treated with PCV (12 years) compared to those treated with TMZ (4.7 years). PFS [HR = 0.46, p = 0.04] and OS [HR = 0.26, p = 0.04] were significantly longer in those receiving PCV-based treatment compared to TMZ-based treatment. After adjusting for previously mentioned variables, Cox regression analysis revealed no difference in OS between PCV- and TMZ-based treatment. The overall adverse effect rate did not significantly differ between PCV-based and TMZ-based treatment (25% vs. 28.1%, p > 0.99).

CONCLUSIONS:

PCV treatment confers longer progression-free survival than TMZ treatment for oligodendroglioma patients, noting that most patients in our series received concurrent radiation with TMZ, and those receiving PCV not having received upfront radiation. As we anticipate the results of the CODEL trial, our findings suggest PCV-based therapy warrants consideration as the preferred therapeutic option for oligodendroglioma patients.
1248 Optimal Connectivity Map Predicts Seizure Freedom Rates After Laser Interstitial Thermal Therapy in Mesial Temporal Lobe Epilepsy
Authors: Kim Min Jae , Hwang Brian Y. , Mampre David Michael , Negoita Serban , Tsehay Yohannes , Kang Joon , Anderson William S.
Published: March 2024

INTRODUCTION:

Laser Interstitial Thermal Therapy (LiTT) is increasingly becoming a first-line surgical therapy for mesial temporal lobe epilepsy (mTLE). While promising, its seizure outcomes have also been highly variable, presumably due to an incomplete understanding of mechanisms behind LiTT. Epilepsy is a network disorder, and therefore it is crucial to account for both the effect on local destruction of epileptogenic foci, as well as global intervention of limbic circuitry, to elucidate the circuit-level mechanisms of LiTT and devise improved ablation strategies. In this study, we explore LiTT's network-level effect by investigating functional connectivity patterns and identifying optimal connectivity patterns predictive of seizure freedom.

METHODS:

27 mTLE patients who underwent unilateral LiTT were classified as seizure-free (ILAE Class I) or seizure-present (ILAE Class II–VI) cohort based on one-year postoperative outcomes. Individual ablation volumes were segmented from intraoperative MRI sequences. Ablation volumes were seeded into a normative functional connectome (Brain Genomics Superstruct Project) to extract patient-specific connectivity profiles associated with ablation volumes. FC patterns were compared between the two cohorts to produce voxel-wise “t-maps” to identify local and global differences in connectivity strengths predictive of seizure freedom.

RESULTS:

Ten mTLE patients achieved complete seizure freedom. In seizure-free patients, right ablated volumes shared higher FC with regions such as calcarine, cuneus, and thalamic anterior pulvinar nucleus than patients with seizure presence.

CONCLUSIONS:

For the right-sided ablations, seizure freedom was associated with a distinctive whole-brain connectivity pattern beyond the local surgical target. Further investigation is required to explore if this pattern is specific between the two surgical sides in mTLE population.
1249 Single-Center Outcomes of Onyx Frontier and Resolute Onyx Drug-Eluting Balloon Mounted Stents for Rescue Stenting for Acute Large Vessel Occlusion
Authors: Mehta Shyle , White Timothy G. , Werner Cassidy , Shah Kevin , Teron Ina , Link Thomas W. , Patsalides Athos , Woo Henry H.
Published: March 2024

INTRODUCTION:

Mechanical thrombectomy (MT) is a common treatment for large vessel occlusions with recent literature expanding its indications. In cases where MT fails, rescue stenting may be necessary to achieve reperfusion; however, the absence of standardized techniques or devices poses a challenge.

METHODS:

A retrospective chart review was performed of all patients who underwent rescue stenting, in the setting of MT, using Onyx Frontier or Resolute Onyx stents at a single institution. Technical details, procedural complications, and patient outcomes were recorded for each case.

RESULTS:

In total, 21 Onyx Frontier and Resolute Onyx stents were deployed in 18 patients undergoing rescue stenting. Among these, 13 involved the use of Resolute Onyx stents, while 5 cases utilized Onyx Frontier stents. Stent locations included the middle cerebral artery (40%), internal carotid artery (15%), vertebral artery (20%), and basilar artery (25%). The average NIHSS score before MT was 13.83 (range 0-31). The median initial mRS score was 0, while the median mRS score at follow-up was 3. Successful reperfusion, as assessed by TICI scores, was achieved in 43.8% of patients for TICI 3, 43.8% for TICI 2C, and 12.5% for TICI 2B. The average proximal vessel diameter was 2.31 mm, and the most used stent length was 12 mm. Post-revascularization, 33% of patients experienced hemorrhage, of which only one patient (16.7%) had symptomatic hemorrhage due to vessel rupture necessitating hemicraniectomy.

CONCLUSIONS:

Onyx Frontier and Resolute Onyx stents are well-suited for rescue stenting in cases where aspiration and stentriever techniques fail during MT. These balloon-mounted drug-eluting stents exhibit excellent navigability, rendering them appropriate for rescue revascularization procedures. Our findings demonstrate that these stents confer a high degree of technical success and a low rate of intra- and post-procedural complications.
125 Contribution of Sensory Neuron-associated Macrophages to Neuropathic Pain via Up-regulation of Calcium Channel in C Fiber Sensory Neurons in Dorsal Root Ganglion: An Animal Model Study
Authors: Kim Keonhee , Jung Eunyee , Chung Seungsoo , Shin Dong Ah
Published: March 2024

INTRODUCTION:

Animal models have demonstrated that sensory neuron-associated macrophages (sNAMs) play a key role in the initiation and persistence of neuropathic pain. The Cav3.2 calcium channel (Cav3.2) is also known to be involved in modulating neuropathic pain in peripheral sensory neurons.

METHODS:

Male Sprague-Dawley rats underwent unilateral tight ligation of the lumbar 5 spinal nerve and were divided into three groups: a control group (SHAM), a group that underwent ligation without, and with minocycline (SNL and SNL+Mino). The mechanical pain threshold of the hind paw was assessed with von-Frey filament application. Immunohistochemical staining techniques were used to evaluate the levels of sNAM, Cav3.2, and C-fiber sensory neurons with anti-Iba1, anti-Cav3.2, and IB4 antibodies, respectively. Cytokine levels were analyzed using cytokine arrays and western blotting.

RESULTS:

The SNL group had a significantly lower pain threshold compared to the control group (p < 0.001). In the DRG, neuropathic pain led to an accumulation of macrophages and increased their ability to attach to Cav 3.2. The expression of Cav 3.2 then triggered the activation of IB4 cells in the DRG. Additionally, cytokine array and western blot analyses revealed a higher expression rate of TNF-α in the SNL group compared to the control group (p = 0.048). Treatment with minocycline resulted in increased pain threshold, decreased number of macrophages in the DRG, and interruption of the attachment between macrophages and Cav 3.2, leading to lower expression of TNF-α.

CONCLUSIONS:

In conclusion, the results of this study suggest that sNAMs may play a role in the development of neuropathic pain by increasing the expression of Cav3.2 through the upregulation of TNF-α release in peripheral sensory nociceptive neurons.
132 Optimizing Success Rates of CSF Liquid Biopsy Examined With Next Generation Sequencing in Pediatric Central Nervous System Tumors
Authors: Chapman Nicholas , Chiarelli Peter , O'Halloran Katrina , Biegel Jaclyn , Krieger Mark D.
Published: March 2024

INTRODUCTION:

Cerebrospinal fluid (CSF) liquid biopsy presents an attractive option for minimally invasive diagnosis and follow up for pediatric brain tumors. Best practice for obtaining appropriate cfDNA for next generation sequencing (NGS) is not currently known.

METHODS:

CSF was collected from patients under a prospective study to evaluate diagnostic utility of NGS. Samples were collected from control (non-tumor) and CNS tumor patients. CSF was collected at the dura opening, immediate ventricular catheter (IVC) from CSF divergent procedures, or ventricular shunt taps. Data was gathered on demographics, pathological diagnosis, tumor location, volume of CSF extraction, and DNA yield.

RESULTS:

CSF was extracted from 72 CNS tumor patients and 20 controls (48 female, 44 male). Of the CNS tumors, there were forty low-grade tumors (40/72) and thirty-two high-grade tumors (32/72). CSF collection location included dura opening (57), ventricular catheter (23), and shunt taps (12). cfDNA yield (ng) for CNS tumors displayed a mean of 135.5 ng (±353.4) and controls displayed a mean of 95.6 ng (±241.0). CNS tumor patients generated a significantly higher (p < 0.0001) DNA concentration (ng/cc) with a mean of 18.9 ng/cc (±82.7) compared to 0.5 ng/cc (±0.7) mean for controls. High grade tumors demonstrated a significantly greater amount of cfDNA concentration with a mean of 33.6 ng/cc (±116.6) whereas low grade tumors had a mean of 4.2 ng/cc (±5.0). CSF acquisition was 90.2% successful for NGS with a mean volume of 4.9 cc. In addition, infratentorial tumors revealed a 96% success rate with a mean volume of 5 cc.

CONCLUSIONS:

Extracting 4.9 cc of CSF had an 90.2% success rate for NGS. CSF may be acquired from either ventricular catheter or dura opening. High grade tumors had significantly higher cfDNA yield and concentration in CSF compared to low grade.
135 Guillain-Barré Syndrome After COVID-19 Vaccination: A Systematic Review and Analysis of Case Reports
Authors: Jamal Taha Mohammad Jehad , Falah Obaida , Hammad Elsayed Mohamed , Kozaa Yasmeena Abdelall , Taha Ahmad J. , Sameer Shams Khalid , Alrubasy Warda A. , Abuawwad Mohammad T.
Published: March 2024

INTRODUCTION:

Cases of Guillain-BarrÉ Syndrome (GBS) have been believed to be associated with the novel COVID-19 infection, and also with the following vaccines developed against the infection.

METHODS:

An electronic search was conducted through four databases: PubMed, Scopus, medRxiv, and Google Scholar for all case reports after COVID-19 vaccine administration. Differences between groups were assessed by Pearson chi-square test. Modified Erasmus GBS Outcome Score for the ability to walk after GBS was calculated for all cases with sufficient clinical data, and Kaplan-Meier survival analysis was performed to study the effect of vaccine type on the relationship between vaccination time and complication of GBS.

RESULTS:

175 cases of GBS following COVID-19 vaccination were included. The Acute Inflammatory Demyelinating Polyradiculoneuropathy subtype was the most reported subtype with 74 cases (42.29%). The affected age group averaged around 53.59 ± 18.83 years, with AMSAN occurring in a rather older group (63.88 ± 20.87 years, p = 0.049). The AstraZeneca vaccine was associated with AIDP (n = 38, 21.71%) more than other vaccines, p = 0.02. The bilateral facial palsy subtype was mostly linked to adenoviral vector vaccinations, accounting for an average of 72% of the total BFP cases. Most GBS patients survived (96%, p = 0.036), however, most patients had low mEGOS scores (4 ± 3.57, p < 0.01). On average, patients developed GBS at 13.43 ± 11.45 days from vaccination (p = 0.73), and survival analysis for complication of GBS into mechanical ventilation or walking impairment yielded a severely increased probability of complication after 25 days (p < 0.01).

CONCLUSIONS:

Guillain-BarrÉ Syndrome can manifest after COVID-19 vaccination. Most cases occurred after receiving the AstraZeneca vaccine, and despite low mortality rates, ambulation was compromised in most patients. A higher risk of GBS complication is associated with an onset later than 12-13 days, particularly with Pfizer, AstraZeneca, and Moderna vaccines.
136 Initial Clinical Safety and Feasibility From the RESET RA Study of a Novel Implantable Neuroimmune Modulation Device for the Treatment of Rheumatoid Arthritis
Authors: Peterson Daniel L. , Van Poppel Mark Daniel , Boling Warren , Santos Perry , Schwalb Jason M. , Eisenberg Howard , Mehta Ashesh , Spader Heather , Botros James , Vrionis Frank D. , Ko Andrew , Adelson P. David , Lega Bradley Charles , Konrad Peter , Calle Bill , Bucholz Richard D. , Richardson Robert Mark
Published: March 2024

INTRODUCTION:

Electrical stimulation of the vagus nerve activates the inflammatory reflex to inhibit cytokines and decrease clinical signs and symptoms of chronic inflammatory disease such as rheumatoid arthritis (RA) (Genovese et al. Lancet Rheum 2020).

METHODS:

The device system consists of two implanted components: a miniature integrated pulse generator and a silicon sleeve positioning device that holds the generator in apposition to the nerve. There are two external components: a wireless charger and an iPad application for programming the pulse generator. Subjects were randomly assigned (1:1) after device implantation on the left vagus nerve to receive active or sham stimulation. The risks of the surgical procedure, device, and stimulation were blindly assessed after 12 weeks of stimulation therapy in the first 60 subjects enrolled in the study.

RESULTS:

All implant procedures were completed without intraoperative complications, infections, or surgical revisions. No unanticipated adverse events (AEs) were reported during the perioperative period and at the end of 12 weeks of follow-up. No serious AEs related to the device, stimulation, or explant procedures were reported. Vocal cord paresis and prolonged hoarseness were reported in two subjects. The former resolved following vocal cord augmentation with injectable filler; the latter is ongoing and improving with speech therapy.

CONCLUSIONS:

Initial results demonstrated that implantation and programming of the novel neuroimmune modulation device were safe, and the surgical procedure and device were well tolerated.
140 Muscle Accelerometry as a Novel Marker of Axonal Injury in Chronic Entrapment Neuropathy
Authors: Javeed Saad , Xu Yameng , Benedict Braeden Christopher , Yan Ying , Birenbaum Nathan , Zhang Justin , Dibble Christopher , Greenberg Jacob K , Faraji Amir H. , Spinner Robert J. , Brogan David , MacEwan Matthew R. , Ray Wilson Zachary
Published: March 2024

INTRODUCTION:

Chronic entrapment neuropathy results in a clinical syndrome ranging from mild-pain to debilitating atrophy. There remains a lack of objective metrics that quantify nerve dysfunction and guide surgical decision-making. Muscle accelerometry quantify mechanical-motor-activity after stimulation of neuromuscular tissue and may enable evaluation of underlying nerve function.

METHODS:

Experimental Lewis-rats underwent compressions at proximal- and distal-sites of sciatic nerves using silicone-conduits. To simulate chronic-entrapment, sciatic nerves were compressed for 2-, 3-, and 4-months (n = 6 in each month) and were serially evaluated by accelerometry, compound-muscle-action-potential (CMAP), and compound-neural-action-potential (CNAP). To simulate recovery, sciatic nerves were decompressed at 3-months and tracked for additional 2-months with accelerometry, CMAP, and CNAP. In each group, the left-side served as control nerve and right-side served as experimental nerve. Accelerometry was acquired by custom-built-device after direct electrical-nerve-stimulation from 0.1-mA to 1.5-mA current. The accelerometry was quantified by composite magnitude of muscle movement in x-, y-, and z-axis. At each endpoint, histomorphometry analysis was performed to evaluate nerve injury and recovery.

RESULTS:

After each month of nerve compression, there was a trend in worsening of nerve function indicated by decline in accelerometry at higher stimulation current of 1.5-mA .This finding was correlated with CMAP and CNAP.At each endpoint of 2-, 3-, and 4-month, there was significant worsening in g-ratio of compressed nerve as compared to the control nerves. After decompression at 3-months, muscle accelerometry at 0.5 mA current indicated a clear trend in recovery of nerve function. This finding was correlated with CNAP, however, CMAP results were variable.

CONCLUSIONS:

The muscle accelerometry may serve as a quantitative marker of axonal function and neuromuscular reinnervation in chronic entrapment neuropathy.
143 Individual Vagus Nerve Sensory Neurons Respond Distinctly to Specific Pro-inflammatory Cytokines
Authors: Huerta Tomas , Chen Adrian , Chang Eric H.
Published: March 2024

INTRODUCTION:

The peripheral nervous system (PNS) communicates with the immune system in response to injury or infection. In the case of inflammation, sensory signals travel up to the brain via the vagus nerve, which is a major pathway for neuro-immune communication. While our previous work showed that systemic cytokine administration was associated with specific patterns of vagus nerve activity, we did not know how individual vagal sensory neurons encoded this immune information. Here, we use invivo calcium imaging to monitor the neural activity of individual vagal sensory neurons in response to specific inflammatory mediators.

METHODS:

Using mice that express the calcium sensor GCaMP6f in glutamatergic neurons, we imaged neurons of the nodose ganglion in-vivo using a 1-photon miniature microscope (Miniscope). During imaging, the inflammatory mediator tumor necrosis factor (TNF) and interleukin 1β (IL-1β) were applied directly to the vagus nerve. The fluorescence data were analyzed with Python-based calcium imaging analysis (CaImAn) software and customized pipelines to output the neural activity as the normalized change in fluorescence (DFF) individually detected neurons.

RESULTS:

Our results reveal that specific vagal sensory neurons respond differentially to specific immune mediators. The average amplitude, and integral of TNF-responsive neurons were significantly higher than IL-1β-responsive cells (TNF vs IL-1β, p < 0.01). This result suggests that TNF application triggers higher firing rates for a more prolonged time in TNF-responsive neurons compared to IL-1β specific responses. Neuronal responses to IL-1β had a significantly higher number of peaks when compared to TNF responses (IL-1β vs TNF, p < 0.05).

CONCLUSIONS:

Our findings demonstrate that individual vagal sensory neurons encode information about distinct inflammatory stimuli and provide insight into the neural sensing of inflammation. Further investigation into neuro-immune signaling may identify novel neural targets for the treatment of inflammatory disorders.
144 Use of Intraoperative Sodium Fluorescein During Nerve Tumor Surgery: A Systematic Review
Authors: Venero Carmelo , Asfour Mohamed Zaky , Palmisciano Paolo
Published: March 2024

INTRODUCTION:

Nerve tumors are categorized into various classifications based on location, origin, and malignant potential. Symptoms and signs of nerve tumors result from direct infiltration of the nerve, compression on adjacent tissues, or the mass effect of the tumor. The primary treatment approach for nerve tumors is complete surgical resection. This should be achieved while preserving the function of the nerve. Sodium fluorescein holds promise in achieving this objective.

METHODS:

PubMed, EMBASE, Web-of-Science, and SCOPUS were searched to include studies reporting the use of sodium fluorescein in nerve tumors surgery. Intervention-related outcomes were systematically reviewed following the PRISMA guidelines.

RESULTS:

Our review comprised 5 studies encompassing 177 patients with a total of 179 tumors. Of these patients, 98 (55.4%) were female, and 101 (69.1%) had sporadic (non-syndromic) tumors. Histopathological examination revealed that 125 (69.8%) tumors were schwannoma WHO grade 1. No post-operative complications were reported in 149 (88.7%) patients. Gross total resection was achieved in 152 (84.9%) tumors. High tumor fluorescence was reported in 150 (94.3%) tumors, while absent and low parent nerve fluorescence was reported in 121 (79.6%) and 27 (17.8%) tumors, respectively. No side effects of the fluorescent dye were reported among the 179 tumor cases. The median latency period was 30 (range: 7-95) minutes, and the median duration of surgery was 51.5 (range: 24-92) minutes.

CONCLUSIONS:

Intraoperative sodium fluorescein shows promise as an aid in nerve tumor surgery, facilitating differentiation between the tumor, parent nerve, and surrounding soft tissue. Future prospective studies are necessary to determine its effect on surgical duration, postoperative complication rates, and extent of resection in comparison to current standard of care.
148 Ventral Mammillo-tegmental Tract Atrophies With Normal Aging
Authors: Skandalakis Georgios P. , Courville Evan , Owodunni Oluwafemi , Kazim Syed Faraz , Hadjipanayis Constantinos G. , Kalyvas Aristotelis , Yeh Fang-Cheng , Kogan Michael
Published: March 2024

INTRODUCTION:

We recently characterized the Ventral Mammillo-tegmental tract (VMTT) throug Klingler’s microdissections and fiber tractography using an averaged template generated from diffusion MRI (dMRI) data of 1065 human healthy subjects acquired from the Human Connectome Project (HCP) and the 50/200 μm cadaveric brainstem dMRI Duke database. The VMTT interconnects the ventral tegmental area with mammillary bodies, regions that are profoundly affected in dementia. We hypothesize that his tract is involved in memory which is inherently affected by normal brain aging and thus atrophy over time.

METHODS:

We performed fiber tractography of the VMTT and the corticospinal tract (CST), using individual subject data from multiple HCP databases spanning neonatal, developmental, healthy adult, and aging populations. These data were generated using an averaged template from diffusion MRI (dMRI) data of 1065 healthy human subjects acquired from the Human Connectome Project (HCP) and the Duke database of cadaveric brainstem dMRI. The CST served as a control in this study. Tract diameter, volume, and fractional anisotropy were measured using DSI Studio developed by FCY. Trends analysis was performed evaluating diameter changes by age.

RESULTS:

The tract was reconstructed in total of 20 subjects for ages ranging from 9 to 100 years old. Our analysis revealed a significant age-related atrophy of the VMTT (p < 0.0001) while no age-related atrophy was observed in the CST (p = 0.161).

CONCLUSIONS:

Our findings indicate that the VMTT experiences disproportionate atrophy with normal aging as compared to CST which served as a control tract. This highlights the distinct age-related changes in the VMTT. Future dMRI studies on this tract across diverse patient populations will shed light on its potential role as a biomarker for early diagnosis of dementia disorders and its utility as a deep brain stimulation (DBS) target.
149 Dynamical Network State Sequences for Human Language Production
Authors: Forseth Kiefer , Pitkow Xaq , Fischer-Baum Simon , Tandon Nitin
Published: March 2024

INTRODUCTION:

Speech requires the selection of a conceptual representation, the construction of a word form, and the execution of a complex articulatory plan. Investigating this global system requires high-resolution recordings with an analytic approach to resolve discrete cognitive states. We integrated autoregressive hidden Markov models to resolve trial-by-trial state transition sequences in distributed networks derived from a large-scale electrocorticographic dataset with complete coverage of language-dominant cortex.

METHODS:

Intracranial electrodes (n = 25810, 134 patients), including both surface grids and stereotactic depths, were implanted for the evaluation of epilepsy. Patients performed picture naming of common objects and underwent systematic cortical stimulation mapping of language function. We used cross-validated autoregressive hidden Markov models – combining the interpretability of multivariate autoregressive analysis with the nonlinear embedding of the switching Markov characteristic – to distinguish cognitive states defined by causal interactional motifs of distributed cortical substrates and to simulate in silico lesions of dynamical network structures.

RESULTS:

We created a detailed spatiotemporal atlas of word production spanning the entire language-dominant cortex. From this map, we resolved network dynamics comprising sequences of state space transitions for each word articulated. This identified five essential states for speech production, each defined by a unique pattern of directed interactions within the language network. We then derived a computational lesion model for state dynamics and compared its predictions with causal perturbation by direct cortical stimulation. We assembled a global dynamical state model for language production and resolved the fine-scale interregional dynamics of conceptualization and lexical access.

CONCLUSIONS:

The distributed network dynamics detailed within this comprehensive interactional map of speech production advance our understanding of how both local and disconnection injuries yield complex neurological deficits, facilitating the development of novel therapeutic approaches for aphasia.
153 Spatial Transcriptomic Profiling of T Cell Exhaustion Markers in Atypical Teratoid Rhabdoid Tumor Subtypes
Authors: Lucke-Wold Brandon
Published: March 2024

INTRODUCTION:

Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in pediatric populations. Despite advances in treatment, overall survival remains poor and novel effective therapies are needed.

METHODS:

Tumor purities of 49 atypical ATRT tumors, encompassing 3 epigenetic subtypes (MYC, SHH, TYR) were estimated using known mRNA expression signatures of stromal and immune cells. Using the purity estimates and bulk tumor expression values, non-negative linear regression was implemented to estimate the average expression of each gene in the stromal and tumor compartments for each subtype.

RESULTS:

Compared to other subtypes, SHH-ATRTs expressed relatively higher levels of T-cell immunoglobulin domain and mucin domain protein 3 (TIM-3) and its ligand GAL9. MYC-ATRTs expressed higher levels of numerous T cell inhibitory receptors including lymphocyte activation gene 3 protein (LAG-3), band T lymphocyte attenuator (BTLA), cytotoxic T lymphocyte antigen-4 (CTLA-4), and programmed cell death protein 1 (PD-1).

CONCLUSIONS:

The predicted stromal and tumor compartment deconvolution yielded previously unrecognized expression patterns of T cell exhaustion markers which should be evaluated further to develop effective targeted therapies for ATRT.
154 Elucidating the Immune Landscape of Radiation Necrosis Through Single Cell Analysis of Recurrent Brain Lesions in Patients After Stereotactic Radio Surgery
Authors: Robert Stephanie , Kiziltug Emre , Lu Benjamin , Arnal-Estape Anna , Nguyen Don , Chiang Veronica
Published: March 2024

INTRODUCTION:

Radiation necrosis (RN), a common and morbid side effect of radiosurgical treatment of brain metastasis, is becoming more prevalent as immunotherapy options and patient survival improve. Thought to be immunologically driven, the pathophysiology of RN remains poorly defined. Further, RN is often indistinguishable from regrowing metastases after stereotactic radiosurgery (SRS), requiring invasive brain biopsy for diagnosis.

METHODS:

We collected 20 intraoperative samples from patients undergoing craniotomy for RN and/or metastatic tumor, as well as time-matched blood and CSF. We created a tissue bank, processed samples, and using fluorescence-activated cell sorting (FACS) and 10x Genomics single cell RNA sequencing, analyzed the cellular immune profile of lesional tissue, blood, and CSF.

RESULTS:

RN tissue demonstrates a robust, detectable expression of immune cells, including CD8+ and CD4+ T cells, natural killer (NK) and myeloid cells. Importantly, clustering of RN-derived immune cells (including T cells, myeloid cells, and NK cells) is reflected in the blood and CSF, with similar immune profiles. We demonstrate a subpopulation of myeloid cells with a microglia signature (CD14+, LYZ-, MS4A7+), and a separate population expressing interferon-stimulated gene (ISG). Supporting these findings, pathway analysis of top blood markers reveals pathways involved in innate and inflammatory immune responses in the blood of RN patients.

CONCLUSIONS:

These findings demonstrate the feasibility of extracting live cells from RN tissue for scRNAseq analysis and suggest that there are unique signatures of RN that can be detected in the blood and CSF of patients. This work has the potential to open new avenues for improved diagnostic and therapeutic approaches to allow earlier detection and more effective treatment of RN in patients with metastatic brain tumors.
155 Safety and Efficacy of Endovascular Versus Microsurgical Treatment of Unruptured Wide-necked Middle Cerebral Artery Aneurysms: A Propensity-Matched Analysis of the Neurovascular Quality Initiative-Quality Outcomes Database (NVQI-QOD)
Authors: Padmanaban Varun , Zhu Junjia , Zhou Shouhao , Ansari Sameer , Howington Jay , Sahlein Daniel , Tejada Juan , Wilkinson D. Andrew , Simon Scott Douglas , Cockroft Kevin M. , Church Ephraim W.
Published: March 2024

INTRODUCTION:

There is clinical equipoise regarding the best treatment for unruptured wide-necked middle cerebral artery (WN-MCA) aneurysms.

METHODS:

The NVQI-QOD registry was queried for patients with unruptured WN-MCA aneurysms. Wide-neck was defined as aneurysm neck = 4 mm or dome:neck ratio = 2. Demographics, aneurysm characteristics, and safety data were queried. Aneurysm occlusion status and modified Rankin score (mRS) at discharge and last follow up were evaluated. Propensity score matching was utilized to match aneurysm size, number of aneurysms treated, patient age and aneurysm status (asymptomatic or symptomatic).

RESULTS:

Of 670 unruptured MCA aneurysms, 319 were wide-necked. Thirty operations were excluded as the aneurysm was previously treated. 289 operations in 282 patients were assessed (203 EVT, 86 MS). After propensity score matching, there were 86 operations in each group. The median aneurysm size was 5.6 mm (EVT) versus 5.3 mm (MS), p = 0.243. Patients who underwent MS were more likely to have complete occlusion at discharge (90.4% vs. 58.8%, p < 0.001). The median follow up was 404 days in the EVT group versus 157.5 days in the MS group (p = 0.241). Patients who underwent EVT were more likely to have a mRS of zero at discharge (50/59 (84.8%) versus 29/54 (53.7%), p < 0.0003) and last follow up (36/55 (65.5%) versus 13/36 (36.1%), p = 0.006). Safety data showed similar intra-operative (7% EVT vs. 3.5% MS, p = 0.496) and post-operative (4.7% EVT vs. 7% MS, p = 0.750) complication rates.

CONCLUSIONS:

This report describes the largest-to-date, modern cohort of propensity matched patients undergoing treatment of unruptured WN-MCA aneurysms. Patients undergoing EVT had better functional outcomes at discharge and last follow up though there was significant loss to follow up. Patients undergoing MS were more likely to have complete aneurysm occlusion. Safety data was similar in both groups.
162 The New Military Neurosurgeon Readiness Metric to Assess Surgical Readiness and Deployability
Authors: Woodle Samuel , Dewar Callum , Hooten Kristopher G.
Published: March 2024

INTRODUCTION:

The US Military Health System includes military treatment facilities (MTFs) and deployable medical providers that have a dual mission to provide a “medically ready force and a ready medical force”. During wartime, the surge in casualties provides abundant surgical case volume to train and sustain a ready medical force. In contrast, peacetime poses a major challenge to military provider readiness, where lessons learned are quickly forgotten and advancements in trauma and combat surgical care decelerate; a phenomenon coined the “Walker dip”. As such, the Defense Health Agency in 2019 mandated critical wartime specialties develop specialty-specific readiness metrics to measure and maintain skills and competencies, named Knowledge, Skills, and Abilities (KSA). The neurosurgery KSA metric was released in early 2023.

METHODS:

Case counts and associated KSA values were obtained for active duty (AD) military neurosurgeons and neurosurgery-capable MTFs over the last 12 months.

RESULTS:

The neurosurgery KSA metric is a point-based system that assigns case valuations based on five categories: cranial (70 points), spine (45), peripheral (15), endovascular (5) and minor (5). The threshold KSA value per provider is set at 8000 points annually, or 667 monthly. Threshold was selected as the average between the KSA of a typical level II trauma center annual case volume and initial ABNS certification caseload requirements. Of 51 AD neurosurgeons from 16 MTFs over a 12-month period, only three providers have monthly KSA values above threshold; all of which have duty assignments at civilian institutions.

CONCLUSIONS:

Less than 10% of AD military neurosurgeons are meeting readiness thresholds per the KSA metric. However, no internal/external validation has been performed. Future validation studies will be pivotal in determining metric accuracy and guide adjustments to ensure a medically capable military force.