bluuebunny/crossref_metadata_2025 huggingface dataset:
Recognizing and Maximizing the Nexus of Perioperative Medicine and Narrative Medicine
Authors: Vetter Thomas R.
Published: March 2023

Perioperative medicine remains an evolving, interdisciplinary subspecialty, which encompasses the unique perspectives and incorporates the respective vital expertise of numerous stakeholders. This integrated model of perioperative medicine and care has a wide-ranging set of clinical, strategic, and operational goals. Among these various programmatic goals, a subset of 4, specific, interdependent goals include (1) enhancing patient-centered care, (2) embracing shared decision-making, (3) optimizing health literacy, and (4) avoiding futile surgery. Achieving and sustaining this subset of 4 goals requires continued innovative approaches to perioperative care. The burgeoning field of narrative medicine represents 1 such innovative approach to perioperative care. Narrative medicine is considered the most prominent recent development in the medical humanities. Its central tenet is that attention to narrative—in the form of the patient’s story, the clinician’s story, or a story constructed together by the patient and clinician—is essential for optimal patient care. If we can view the health care experience through the patient’s eyes, we will become more responsive to patients’ needs and, thereby, better clinicians. There is a potential clinical nexus between the perioperative medicine practice and narrative medicine skills, which, if capitalized, can maximize perioperative patient care. There are a number of untapped educational and research opportunities in this fruitful nexus between perioperative medicine and narrative medicine.
Understanding Outcomes After Major Surgery
Authors: Harvie David Alexander , Levett Denny Zelda Hope , Grocott Michael Patrick William
Published: March 2023

The global volume of surgery is increasing. Adverse outcomes after surgery have resource implications and long-term impact on quality of life and consequently represent a significant and underappreciated public health issue. Standardization of outcome reporting is essential for evidence synthesis, risk stratification, perioperative care planning, and to inform shared decision-making. The association between short- and long-term outcomes, which persists when corrected for base-line risk, has significant implications for patients and providers and warrants further investigation. Candidate mechanisms include sustained inflammation and reduced physician activity, which may, in the future, be mitigated by targeted interventions.
Trans (In)Visibility in Art
Authors: Thompto Chelsea
Published: March 2023

Through an examination of how the art world engages with transness, the piece begins with an exploration of why we need an understanding of trans subjectivity that is not beholden to or subsumed by the art world's overriding attention and interest in queer subjectivities and concerns. The author then describes how trans methodologies are applied within their artistic and curatorial practice and how those methodologies are situated within the broader context of the art world. Particular focus is given to codes as both the subject (social, governmental, and technical codes) and medium (visual and computer codes) of the author's work.
103 Cerebrospinal Fluid Drainage in Acute Spinal Cord Injury: A Multi-Center, Randomized, Controlled Trial
Authors: Theodore Nicholas , Martirosyan Nikolay L. , Hersh Andrew , Ehresman Jeff , Ahmed Ali Karim , Danielson Jill , Sullivan Cindy , Shank Christopher D. , Almefty Kaith K. , Lemole G. Michael , Kakarla Udaya K. , Hadley Mark N.
Published: March 2023

INTRODUCTION:

The devastating sequelae of spinal cord injury (SCI) are worsened by ischemia and inflammation that occur following the primary mechanical damage to the cord. Optimizing spinal cord perfusion pressure (SCPP), calculated as the difference between mean arterial pressure (MAP) and intrathecal pressure (ITP), may improve long-term neurological outcomes. MAP augmentation is frequently used to improve perfusion; however, the efficacy of ITP reduction is less clear.

METHODS:

Patients with acute cervical SCI presenting within 24 hours were screened for eligibility. All patients received lumbar drain placement and appropriate decompressive surgery. Patients in the control group received MAP elevation only, while patients in the interventional group received MAP elevation and CSFD for a target ITP of below 10 mm Hg for 5 days. ITP and MAP were recorded hourly. Patients underwent functional assessments at enrollment, 72 hours, 90 days, and 180 days after injury.

RESULTS:

A total of 11 patients were enrolled, and four were randomized to receive CSFD. Patients in the CSFD cohort had a mean ITP of 5.3 ± 2.5 mm Hg compared to 15 ± 3.0 mm Hg in the control group. SCPP improved significantly from 77 ± 4.5 mm Hg in the control group to 101 ± 6.3 mm Hg in the experimental group (p < 0.01). Total motor scores improved by 15 ± 8.4 points and 57 ± 24 points in the control and CSFD groups, respectively, over 180 days. No adverse events were attributable to CSFD.

CONCLUSIONS:

CSFD is feasible and an effective mechanism for reducing ITP and improving SCPP in the acute period after SCI. The complication profile was similar between both groups, and long-term improvements in motor and sensory function were seen with CSFD.
108 A Novel Robotic-Assisted Platform for Spinal Decompression Procedures
Authors: Simaan Ranin , Eastlack Robert , Khoo Larry T. , Smith William Douglas , Ellegala Dilantha B. , Ashkenazi Ely , Harel Ran , Millgram Michael
Published: March 2023

INTRODUCTION:

Removal of pathologic tissue during degenerative spinal surgery cases near a bone-nerve interface presents a challenge during spinal decompression, especially in minimally invasive procedures. Robotic systems for spinal surgeries can potentially offer greater accuracy than manual operations. However, today’s robotic systems are designed only for placement of fusion hardware and lack the ability to work in-situ and in proximity to neural structures.

METHODS:

In the proposed approach, the surgeon utilizes a 6-degrees-of-freedom joystick to control an industrial grade robotic arm connected to curved-at-the-tip high-speed, shielded drilling end-effectors to perform various bone removal tasks. Live visual feedback is displayed from top-view and endoscopic camera views. Force readouts, correlated to the force exerted on the end-effector through tissue contact, provide real time visual feedback. Additional safety restrictions are designed into the system to prevent excessive force. System orientation training was conducted on vertebral models. Initially, three spine surgeons used the system to perform ipsilateral decompression and foraminotomy in four surgeries in a live pig model. Next, six surgeons used the system to perform ipsilateral decompression on two human cadavers. All surgeons completed questionnaires assessing procedure efficacy and system usability.

RESULTS:

Animal studies: Required decompression was achieved in all cases, with no complications and minimum-to-moderate bleeding. Intuitive usability and acceptable kinematic range of motion of the robotic system was confirmed. Cadaver study: Questionnaire results demonstrated high scores of confidence in the technique (4.7/5), overall satisfaction (4.4/5) and achievement of adequate decompression (3.9/5). All neural structures remained intact.

CONCLUSIONS:

This preliminary data indicates that the proposed robotic system can facilitate safe and precise decompression through removal of sufficient tissue removal at the bone/nerve interface. Further studies with a medical grade robotic arm are planned.
113 The Use of Machine Learning of Carotid Web Angioarchitecture for Predicting Stroke Risk
Authors: von Oiste Grace , Narayan Vinayak , Moin Mustafa Nasir , Raz Eytan , Shapiro Maksim , Rutledge Caleb , Nelson Peter Kim , Riina Howard A. , Oermann Eric , Nossek Erez
Published: March 2023

INTRODUCTION:

Carotid webs (CWs) are a known mechanism for stroke in young adults without other vascular risk factors. Altered hemodynamics distal to the web may cause flow stagnation with the potential for distal embolization of clots. Although there are some computational flow models studies of CW, currently there are no well-described CT angiographic features to predict stroke risk.

METHODS:

Anatomical data of the internal carotid artery (ICA), common carotid artery (CCA), the CW and its “distal pouch” angioarchitecture was gathered as part of a retrospective cohort study from symptomatic (stroke) and asymptomatic (non-stroke) patients. Principal component analysis was applied to anatomical and angioarchitectural features, and the two components were plotted to investigate whether the stroke and non-stroke patients were easily separable. We built a predictive model of stroke risk using these features with Firth regression to reduce bias related to small datasets.

RESULTS:

The first two principal components of the anatomical and angioarchitectural features clearly distinguish between stroke patients and non-stroke patients. The firth regression and 5-fold cross validation revealed that CCA web “pouch” angle (p=.014), ICA web “pouch” tip angle (p=.023), CCA web “pouch” tip angle (p = .017), and ICA web “pouch” angle (p = .016) are the most important features to model and assess stroke risk. Conversely, CCA and ICA anatomy (diameter and angle) on their own were not found to be risk factors for stroke. Overall, pouch angles in respect to flow trajectory in the CCA and in the ICA are significant risk factors as compared to vessel sizes and flow relationships between them.

CONCLUSIONS:

This study demonstrates that carotid web angioarchitecture and carotid anatomy data from diagnostic angiography may be used to assess stroke risk, allowing physicians to tailor care for each patient according to risk stratification.
131 Hedgehog Signaling Mediates Astrocytic Response and Blood-Brain Barrier Repair Following Traumatic Central Nervous System Injury
Authors: Rallo Michael Stephen , Wang Hui , Xu Zhiyan , Matise Michael , Schoeffler Eve
Published: March 2023

INTRODUCTION:

Injury to the central nervous system (CNS) provokes a multicellular response to facilitate restoration of tissue homeostasis. Astrocytes consolidate at the lesion site to form a “glial scar” which restricts leukocyte infiltration and repairs the blood-brain barrier (BBB). However, this “scar” has been considered an impediment to regeneration and functional recovery. Therefore, uncovering molecular regulators that may be therapeutically targeted to promote pro-regenerative astrocyte phenotypes is of great interest.

METHODS:

Genetic reporter and conditional mutant mice were used to monitor, constitutively activate, or ablate Hh signaling following stereotactically-induced penetrating cortical or spinal cord injury. Outcomes including reactive astrocyte proliferation and polarization, leukocyte restriction, and blood-brain barrier repair were assessed via immunohistochemistry.

RESULTS:

Astrocytic expression of the Hh target gene Gli1 was downregulated acutely following injury but restored in the subacute phase. Constitutive activation of Hh signaling reduced astrocytic proliferation (%BrdU/EdU+ = 9.6% vs. 51.0%, p<0.01) and polarization (L/W Ratio = 2.8 vs. 1.5, p < 0.01). Additionally, in the spinal cord, constitutive activation impaired migration and integration of reactive astrocytes into the white matter lesion site. In animals with intact Hh signaling, the BBB recovered by 28 days after injury as evidenced by low levels of plasma protein and leukocyte infiltration. In contrast, conditional ablation of Hh signaling from 14-16 days after injury resulted in persistent BBB defects at 28 days.

CONCLUSIONS:

Our results suggest that acute downregulation of Hh signaling is required to specify reactive astrocyte properties including polarization and cell cycle re-entry. However, restoration of Hh signaling, which occurs subacutely from 10-28 days after injury and coincides with glial scar maturation, is required for leukocyte restriction and BBB repair. Understanding the temporospatial dynamics of postinjury Hh signaling is essential to modeling future therapeutic targets.
134 Retrograde Adeno-Associated Viruses-mediated Gene Transfer to Primary Nociceptors via Paw Injection Modulates Pain-Related Phenotypes
Authors: Unda Santiago R. , Antoniazzi Aldana M. , Norman Sofya , Urien Louise , Marongiu Roberta , Kaplitt Michael Gordon
Published: March 2023

INTRODUCTION:

Primary nociceptors are the first neurons involved in processing normal and pathological pain. Novel biological approaches such as gene therapies targeting these neurons have great potential, but delivery can be challenging when open or percutaneous infusion into the dorsal root ganglion (DRG) is needed.

METHODS:

Primary nociceptors were first targeted unilaterally via right hind paw injection of a retrograde adeno-associated virus serotype 2 (AAVRetro) or a mosaic AAVRetro/rh10 vector encoding a constitutive hM3Dq chemogenetic transgene. A second cohort of mice received the same vectors via unilateral intraneural injection in the right sciatic nerve. Changes in pain-related behaviors were assessed 45-60 min following intraperitoneal administration of the ligand clozapine-n-oxide (CNO) using the Von Frey and Hargreaves tests every other week for 6 weeks post-AAVRetro injection.

RESULTS:

Immunofluorescence and RNA in-situ hybridization of paw injected mice revealed transduction of primary nociceptors in the DRG from L4 to L6 segments, including TrkA, Trpv1, CGRP, and NaV1.8 positive neurons. Chemogenetic activation elicited robust mechanical allodynia responses at 4-week post-RetroAAV delivery in paw injected mice, whilst in sciatic injected mice we observed an earlier pain phenotype starting at 2-week post-RetroAAV administration. No thermal hyperalgesia responses were observed.

CONCLUSIONS:

We demonstrate for the first time that AAVRetro effectively transduces DRG nociceptors via paw injection. Furthermore, chemogenetic activation caused a strong pain phenotype similar to mice injected in the sciatic nerve. These results support further exploration of non-invasive delivery of retrograde viral vectors to modulate pain neurons for potential therapeutic applications.
163 Integrative Genomics Analysis Implicates Decreased FGD6 Expression Underlying Risk of Intracranial Aneurysm Rupture
Authors: Hale Andrew T. , He Jing , Jones Jesse
Published: March 2023

INTRODUCTION:

The genetic determinants of intracranial aneurysm rupture (rIA) are largely unknown. To identify and characterize genetic risk factors for rIA, we perform a genome-wide association study (GWAS) containing 84,353 individuals (7,843 rIA cases and 76,510 controls). We then use functional genomics approaches to delineate the mechanistic consequences of rIA risk loci.

METHODS:

We perform a meta-analysis across 24 published GWAS of rIA. Logistic regression was used to identify rIA-associated single nucleotide polymorphisms (SNPs). Gene-burden, expression quantitative trait loci (eQTL) mapping, and analysis of publicly-available single-cell RNA sequencing (scRNA-seq) data from normal human brain endothelial and perivascular cells was used to delineate cell-lineage expression of rIA-associated genes.

RESULTS:

We identify 5 independent genetic loci reaching genome-wide significance (p < 5.0 x 10-8) for rIA: rs73392700 (CDKN2B, OR = 1.12), rs6841581 (EDNRA, OR = 0.77), rs11661542 (RBBP8, OR=0.84), rs62516550 (RP1, OR = 1.20), and rs12310399 (FGD6, OR = 1.16). FGD6, to our knowledge, has not been implicated in prior GWAS of (r)IA. We then quantified gene-level mutation-burden across ∼20,000 genes, and only FGD6 (containing 21 rIA-associated SNPs) reached transcriptome-wide significance. Functional eQTL mapping indicates that rs12310399 causes decreased FGD6 gene expression in arterial tissue. scRNA-seq identified high expression of FGD6 in 1 of 3 arterial lineages, but absent in perivascular cells, identifying the likely cell-lineage underlying FGD6-mediated rIA risk.

CONCLUSIONS:

We perform the largest genetic study of rIA to date. We identify and characterize a previously unknown risk loci for rIA containing FGD6. Elucidation of high-risk genetic loci may instruct population-genetic screening and clinical-genetic testing strategies to identify patients predisposed to rIA enabling early treatment and improved patient outcomes.
166 The Protective Role of GPR39 in Subarachnoid Hemorrhage
Authors: Mazur-Hart David , Bah Thierno , Siler Dominic Aaron , Pike Martin , Cetas Justin Schultz , Alkayed Nabil
Published: March 2023

INTRODUCTION:

Aneurysmal subarachnoid hemorrhage (SAH) is a devastating stroke with high morbidity and mortality. It causes an early brain injury (EBI), the severity of which can predict delayed cerebral ischemia (DCI). Neuroinflammation is a key component of EBI. The G protein-coupled receptor 39 (GPR39) is expressed in brain, and it has been shown to modulate neuroinflammation.

METHODS:

Endovascular perforation technique induced SAH in GPR39 knockout (KO) and wild-type (WT) littermate mice. Laser-Doppler was used to monitor cortical perfusion before, during, and right after SAH. Body mass and neurological deficit (neuroscore) were assessed daily after SAH. T2-weighted MRI was used to measure ventricular volumes, and T2*-weighted gradient recalled echo (GRE) MRI was used to assess cortical vein engorgement at 24 hours after SAH. Behavioral deficit was assessed using the accelerating rotarod at baseline and on days 2, 3 and 4 after SAH and balance beam on days 2, 3 and 4 after SAH.

RESULTS:

SAH caused an acute, communicating hydrocephalus with engorged cortical veins. WT and KO mice exhibited significant weight loss and deficits in neuroscore after SAH compared to sham mice. GPR39 KO mice had a significantly worse neuroscore than WT mice 3 days after SAH (mean 20.7 vs. 22.3; n = 12 vs. 15, respectively; p = 0.01). Additionally, GPR39 KO mice exhibited worse scores on rotarod 2 days after SAH (mean latency to fall 138.9 vs. 108.8; n=12 vs 15, respectively, p = 0.07) and balance beam 1 day after SAH (mean time to traverse 24.8 vs. 31.8; n = 8 vs. 11, respectively, p = 0.1).

CONCLUSIONS:

Our findings indicate that mice with GPR39 deletion exhibit worse outcomes in neuroscore and sensorimotor domains. These results suggest that GPR39 plays a protective role and may serve as a therapeutic target in SAH.
179 Measuring Real Time Radiation Exposure to Spine-Focused Neurosurgeons
Authors: Chauhan Daksh , Ahmad Hasan Shahzad , Singh Shikha , Albayar Ahmed , Patel Arjun , Welch William Charles , Yoon Jang Won
Published: March 2023

INTRODUCTION:

C-arm fluoroscopy and O-arm navigation are vital tools in modern spine surgeries, but their repeated usage can endanger spine surgeons. While a surgeon’s chest and abdomen are protected by lead aprons, the eyes and extremities generally receive less protection.

METHODS:

This prospective cohort study includes 65 consecutive spine surgeries performed by a single spine-focused neurosurgeon over a 9-month period. Radiation exposure to the primary surgeon was measured through dosimeters worn over the lead apron, under the lead apron, on surgical loupes, and as a ring on the dominant hand. Differences were assessed with rigorous statistical testing and radiation exposure per surgical case was extrapolated.

RESULTS:

During the study, the measured radiation exposure over the apron, 176 mrem, was significantly greater than that under the apron, 8 mrem (p = .0020), demonstrating shielding’s protective effect. The surgeon’s dominant hand was exposed to 329 mrem while the eyes were exposed to 152.5 mrem of radiation. Compared to the surgeon’s protected abdominal area, the hands (p = .0002) and eyes (p=.0002) received significantly greater exposure. Calculated exposure per case was 2.8 mrem for the eyes and 5.1 mrem for the hands. It was determined that a spine-focused neurosurgeon operating 400 cases annually will incur a radiation exposure of 60,750 mrem to the hands and 33,900 mrem to the eyes over a 30-year career.

CONCLUSIONS:

Our study found that spine surgeons encounter significantly more radiation exposure to the eyes and the extremities compared to protected body regions. Lifetime exposure exceeds the annual limits set by the International Commission on Radiological Protection for the extremities (50,000 mrem/yr) and the eyes (15,000 mrem/yr), calling for increased awareness about the dangerous levels of radiation exposure that a spine surgeon incurs over one’s career.
182 Comparison of Post-operative Functional Recovery Following Awake Endoscopic Transforaminal Lumbar Interbody Fusion Versus Lumbar Laminectomy Under General Anesthesia
Authors: Bashti Malek , Basil Gregory , Ahmad Hasan Shahzad , Singh Shikha , Jiao Kenneth , Yang Andrew Il , Jamshidi Aria , Welch William Charles , Wang Michael Y. , Won Yoon Jang
Published: March 2023

INTRODUCTION:

Minimally invasive techniques and awake surgery have changed the nature of fusion surgery, though these effects are not yet fully characterized due to the subjective nature of patient reported outcome measures (PROMs). Physical activity data measured from smartphone accelerometers offer the ability to objectively quantify the benefits of surgical intervention and time to functional recovery.

METHODS:

Patients undergoing single-level open lumbar decompression and awake, endoscopic lumbar fusion under an enhanced recovery after surgery (ERAS) protocol over a 5-year period were eligible for inclusion in this retrospective multi-institution study. Included patients were required to own an Apple iPhone (Apple Inc., Cupertino, CA) and have at least eight months of continuous pre-operative smartphone accelerometer data. Pre-operative demographics and changes in peri-operative activity levels were compared between the two patient groups.

RESULTS:

A total of 33 patients met inclusion criteria, of which 17 underwent awake, endoscopic fusion and 16 underwent open lumbar laminectomy. Fifteen of the 17 patients (88.2%) receiving endoscopic fusion achieved functional recovery within 1 year of surgery. The average length of time to reach functional recovery was 113.8 ± 28.8 days. In comparison, 13 of 16 patients (81.3%) receiving lumbar laminectomy without fusion achieved functional recovery, requiring 105 ± 18.2 days on average. There was no statistical difference in time-to-recovery between groups (p = 0.798).

CONCLUSIONS:

Minimally invasive fusion surgery in the setting of awake spinal anesthesia and peri-operative ERAS protocols allow for a recovery time that is statistically equivalent to post-operative recovery periods of less anatomically invasive decompression surgeries. These findings warrant further investigation and comparison of the functional outcomes of ultra-minimally invasive surgical procedures to traditional standard of care treatments.
188 American Spinal Injury Association (ASIA) Impairment Scale (AIS) Conversion Underestimates Neurological Recovery Following Traumatic Spinal Cord Injury
Authors: Choy Winward , Kyritsis Nikolaos , Fernandez Xuan Duong , Ferguson Adam , Hemmerle Debra P. , Pascual Lisa U. , Singh Vineeta , Talbott Jason , Pan Jonathan , Torres Abel , Whetstone William , Huie J. Russell , Fond Kenneth , Keller Anastasia , Bresnahan Jacqueline , Beattie Michael , DiGiorgio Anthony Michael , Dhall Sanjay S. , Saigal Rajiv
Published: March 2023

INTRODUCTION:

The predominant tool used in the evaluation of neurological outcomes following spinal cord injury (SCI) is the American Spinal Injury Association (ASIA) Impairment Scale (AIS), calculated within the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). However, there are significant clinical and functional differences within AIS grades A-E that can be better captured by ISNCSCI 0-100 full motor scores.

METHODS:

55 patients with acute traumatic SCI who underwent surgery were retrospectively analyzed as part of a prospective cohort study, Transforming Research and Clinical Knowledge in SCI (TRACK-SCI). Clinical, radiographical and treatment parameters were collected, including AIS grades and full motor scores on presentation and discharge, Brain and Spinal Injury Center (BASIC) scores. Multivariable analysis was utilized to evaluate predictors of neurological recovery utilizing AIS grade and motor scores as endpoints.

RESULTS:

Improvement of at least 1 AIS grade from presentation was noted in 27% of patients (mean improvement of 0.3 AIS grades, p < 0.001) upon discharge. Improvement of total motor scores was noted in 67% with a mean recovery of 8.4 points. The discordance between rate of AIS grade conversion and motor score recovery was greatest in patients with initial AIS grade D (16% vs 72%, respectively). Total motor score improvement was greatest for patients with initial AIS grade C, with a mean improvement of 20 points. Utilizing multivariate analysis, BASIC score and initial total motor score were significant predictors of motor score recovery. However, no variables were prognostic when utilizing AIS conversion as the endpoint.

CONCLUSIONS:

AIS conversion underestimates true degree of functional improvement following SCI. Changes in full motor score is a more robust outcome metric in the evaluation of factors prognostic of neurological recovery following injury.
191 Treatment with GM-CSF Reverses TBI-Induced Immune Suppression in a Combined Injury Model
Authors: Sribnick Eric Anthony , Warner Timothy , Hall Mark
Published: March 2023

INTRODUCTION:

Traumatic brain injury (TBI) is a potentially devastating injury for which there are no pharmacotherapies. Frequently, TBI is accompanied by injuries outside the CNS, and we have previously shown that TBI with concurrent extra-cranial injury reliably leads to post-injury immunosuppression, which puts patients at risk for infection and ultimately a poor outcome. To reverse post-injury immune suppression, we have proposed the use of the cytokine granulocyte macrophage colony-stimulating factor (GM-CSF).

METHODS:

To induce post-injury immunosuppression, we used a previously described model. 28 day old rats were injured via controlled cortical impact and then had 25% blood volume removed. Following injury, animals were treated with vehicle, 5 μg/kg, or 50 μg/kg GM-CSF daily for 7 days. Blood was obtained pre-injury, and on 1, 3, and 7 days post-injury. Brain and spleen were harvested at 7 days post-injury. Adaptive and innate immune function (measured by ex vivo cytokine production in response to an immunostimulant) were assessed in blood and spleen. Flow cytometry was performed on blood and spleen samples. Cytokine levels at the lesion and penumbra were measured by ELISA.

RESULTS:

As shown previously, injury induced reduction of both innate and adaptive immune function (approximately 50% decrease), which was reversed with GM-CSF. Treatment with GM-CSF significantly expanded the percentage of monocytes. In spleen, injury was associated with an increase in percentage of CD4 cells expressing programmed death-1 (PD-1), and this was also reversed with GM-CSF. ELISA for cytokines in brain samples from lesion and penumbra from GM-CSF treated animals were not significantly different from vehicle.

CONCLUSIONS:

These data add to a body of literature suggesting that severe trauma leads to immune suppression. Our findings suggest that treatment with GM-CSF may normalize post-injury immune response.
197 A Multidisciplinary Approach to Posterior Quadrant Disconnective Epilepsy Surgery in Pediatric Patients
Authors: Limpo Hiria , Candela Santiago , Hinojosa Jose , Rumia Jordi
Published: March 2023

INTRODUCTION:

Extensive lesions of the posterior quadrant are a relevant cause of pediatric drug-resistant epilepsy. Early surgery is the best treatment in these cases but conventional multilobar resections carry a significant risk in pediatric patients. Despite temporo-parieto-occipital (TPO) disconnection being the preferable technique due to the preservation of motor function, studies reporting long-term longitudinal outcomes are still limited.

METHODS:

A prospective analysis was carried out on 12 children who underwent TPO disconnection. (Image 1 and 2)

RESULTS:

TPO disconnection was performed in 12 pediatric patients aged between 14 months and 18 years (median 6.29 years). The average age of seizure onset was 0.97±1.22 years. Causes of TPO included perinatal ischemia in 4 and malformation of cortical development (MCD) in 8. The presenting seizure types were focal motor impaired awareness seizures in 7 children and generalized in 5. The affected hemisphere was the right one in 9 patients and the left in 3. In half of the patients the temporal approach was performed through T1 and in the other 50% through T2. After neuropsychological examination, 2 children improved, 7 remained stable, 2 patients presented stagnation and 1 declined. Regarding postoperative complications, a non-resorptive hydrocephalus and an asymptomatic caudate nucleus infarct were observed. After a median follow-up of 2 years, 9 patients were in Engel’s Class I seizure outcome.

CONCLUSIONS:

TPO disconnection is a safe and effective motor-sparing epilepsy surgery for children with refractory seizures located in the posterior quadrant, which prevents further cognitive deterioration.
200 Peripheral Nerve Transfer for Spinal Cord Injury: Lower Motoneuron Solutions for Upper Motoneuron Problems
Authors: Jack Andrew Steven , Witiw Christopher , Jacques Line G. , Morhart Michael , Olson Jaret , Chan Ming
Published: March 2023

INTRODUCTION:

Nerve transfers (NTs) have been recognized as a promising strategy to improve traumatic spine cord injury (tSCI) patient function. Although different tSCI NT options have been detailed, little is known about the epidemiological and injury-related aspects of this patient population.

METHODS:

TSCI patients presenting to our institution were identified through a prospectively collected tSCI data registry. Inclusion criteria consisted of: i) admission with cervical tSCI (C1-T1) between 2005-2019, ii);18-years-old, iii) documented tSCI severity using the ASIA Impairment Scale (AIS). Two peripheral nerve (PN) experts independently evaluated each patient’s suitability for NT. Demographic, and traumatic and neurological injury-related variables were collected and analyzed.

RESULTS:

A total of 224 (32%) patients were selected for based on tSCI level (C1-T1). After initial review, there was 94% agreement between PN experts with discordant cases being discussed before reaching a final consensus. A total of 108 patients (15% of tSCIs and 48% of cervical tSCIs) were deemed appropriate NT candidates. Average age was 43-years-old and the majority were male (82/108, 76%). TSCI severity range included: 54 (50%) patients being AIS A, 17 (16%) AIS B, 34 (31%) AIS C, and 3 (3%) AIS D. AIS motor level range included: 7 (6%) C4, 40 (37%) C5, 22 (20%) C6, 38 (35%) C7, and 1 (1%) C8 patient.

CONCLUSIONS:

To our knowledge, this is the first study to detail the number of tSCI patients that may qualify for NT from a large prospective database. A large proportion of cervical tSCI patients were found to be candidates. Better characterizing the epidemiological and injury patterns of this patient population will form an important first step to increase awareness and inform tSCI NT candidate identification.
205 Liquid Biopsy Biomarker for Differentiating Neurofibroma/Schwannoma From Other Solid Mass Mimics
Authors: Patel Neel T. , Khristov Vladimir , Smith Nataliya , Harbaugh Kimberly , Rizk Elias Boulos , Connor James R.
Published: March 2023

INTRODUCTION:

Interleukin13 receptor alpha 2 (IL13Ra2) is a high-affinity receptor for the interleukin 13 (IL13) cytokine. With the exception of the testes, in normal conditions, IL13Ra2 demonstrates little normal cell expression. Prior work in our laboratory has demonstrated that IL13Ra2 is expressed on benign and malignant peripheral nerve sheath tumors in sporadic and syndromic cases. We have shown in in vitro and in murine MPST models that the receptor can be utilized to facilitate the treatment of malignant peripheral nerve sheath tumors. While mice have membrane-bound and soluble forms of IL13Ra2, humans lack the soluble form. We have previously shown the detection of IL13Ra2 exosomes in the cerebrospinal fluid and plasma of patients with glioblastoma.

METHODS:

IL13Ra2 levels were obtained from plasma and tumor specimens of 17 patients with diagnoses of Schwannoma/Neurofibroma (n = 13) and Lipoma/AVM (n = 4). Plasma and Tumor specimens were collected pre-operatively on the day of tumor resection. Plasma levels of IL13Ra2 were measured with ELISA. The tumor specimen was placed in NP40 buffer for extraction then levels were measured with ELISA.

RESULTS:

The plasma level of IL13Ra2 is significantly elevated in patients with schwannoma/neurofibroma compared to patients with lipomas/AVMs. Increased level of IL13Ra2 in tumors correlates with the increased levels of IL13Ra2 in the plasma.

CONCLUSIONS:

Plasma level of IL13Ra2 has the potential for diagnosis and may serve as a liquid biopsy biomarker to help differentiate solid tumors like neurofibroma/schwannoma from lipomas /arteriovenous malformations.
214 Impact of Cochlear Dose on Hearing Preservation Following Stereotactic Radiosurgery in Treatment of Vestibular Schwannomas: A Multi-Center Study
Authors: Klein Andrea Lauren , Chang Steven D. , Muacevic Alexander , Sherman Jonathan H. , Romanelli Pantaleo , Maria Peter Santa , Fuerweger Christoph , Zanetti Isa Bossi , Beltramo Giancarlo , Vaisbuch Yona , Tran Emma , Feng Austin Y. , Teng Hao , Meola Antonio , Gibbs Iris , Tolisano Anthony , Kutz Joe Walter , Wardak Zabi , Nedzi Lucien , MacRae Don , Sohal Preet , Kapoor Elina , Sabet-Rasekh Parisa , Moncada Paola , Zaleski-King Ashley , Monfared Ashkan
Published: March 2023

INTRODUCTION:

Stereotactic radiosurgery (SRS) is a well-established treatment option for patients with vestibular schwannomas (VS). Hearing loss remains one of the main morbidities of VS and its treatments, including SRS. Effects of radiation parameters of SRS on hearing remains largely unknown.

METHODS:

Multicenter retrospective analysis of 611 patients who underwent SRS for VS from 1990 to 2020 and had pre- and post-treatment audiograms.

RESULTS:

Pure tone averages (PTA)s increased and word recognition scores (WRS)s decreased in the treated ears at 12 - 60 months while it remained stable in the untreated ears. Higher baseline PTA, higher tumor radiation dose, higher maximum cochlear dose, and usage of single fraction resulted in higher post radiation PTA; WRS was only predicted by baseline WRS and age. Of these parameters, higher baseline PTA, single fraction treatment, higher tumor radiation dose, and higher maximum cochlear dose resulted in a faster deterioration in PTA. Below a maximum cochlear dose of 3 Gy, there were no statistically significant changes in PTA or WRS.

CONCLUSIONS:

Decline of hearing at 1 year in VS patients after SRS is directly related to maximum cochlear dose, single versus 3-fraction treatment, total tumor radiation dose, and baseline hearing level. The maximum safe cochlear dose for hearing preservation at 1 year is 3 Gy, and the use of 3 fractions instead of 1 fraction was better at preserving hearing.
319 Precision Medicine for Meningiomas: Machine Learning Using Radiomic Feature Analysis Identifies Ki-67 Proliferative Index as a Prognostic Marker of Clinical Outcomes
Authors: Khanna Omaditya , Kazerooni Anahita Fathi , Arif Sherjeel , Baldassari Michael P. , Mahtabfar Aria , Andrews Carrie Elizabeth , Hafazalla Karim , Farrell Christopher James , Evans James J. , Andrews David W. , Shi Wenyin , Davatzikos Christos
Published: March 2023

INTRODUCTION:

An elevated Ki-67 is one crucial factor that influences meningioma behavior. Machine learning(ML) using radiomic feature analysis can identify phenotypic pixel-level imaging signatures for enhanced tumor diagnostics.

METHODS:

Radiomic feature extraction using least-absolute-shrinkage-and-selection-operator(LASSO) wrapped with support vector machine (SVM) through nested cross-validation is used to stratify tumors based on Ki-67 <5% and ≥5%. Clinical outcomes were evaluated based on the predictive power of this algorithm.

RESULTS:

343 patients are included (WHO grade I:291, grade II:43, grade III:9). Overall mean follow-up time is 33.9 months (range: 0-105). The rate of recurrence is 14.4%, 44.2% and 77.8% for grade I, II, and III tumors, respectively. The mean Ki-67% for grade 1, 2 and 3 meningiomas is 4.79+/-3.87 (range: 0.3-33.6), 16.07+/-13.83 (range: 1.5-49), and 35.7+/-13.3 (range: 18-57.4), respectively (p = 0.03). However, there is no difference in tumor and peritumoral edema volumes between meningioma WHO grades 1-3. A total of 46 high-ranking radiomic features were selected to build a ML model. ROC curves for the ML algorithm reveals AUC’s of 0.83 [95% CI: 0.78-0.89] and 0.84 [0.75-0.94] for the discovery (N = 257) and validation (N = 86) cohort, respectively, for classifying Ki-67% based on a 5% cutoff, independent of WHO grade. Kaplan-Meier curves using the ML algorithm reveals decreased progression-free-survival (PFS) for predicted Ki-67 >5% (p < 0.001) for all tumors in the cohort, as well as in sub-analyses of non-skull base tumors (p < 0.001) and skull-base tumors (p < 0.001). A comparison of histopathological PFS versus ML-predicted outcomes based on Ki-67 reveals good concordance for grade I, II and III tumors.

CONCLUSIONS:

ML using radiomic feature analysis can be used to stratify meningiomas based on Ki-67 with excellent accuracy. The predictive power of this model reveals distinctly divergent PFS outcomes, and can be used to guide treatment strategy.
333 Intraventricular Ziconotide Improves Cognitive Outcomes following Lateral Fluid Percussion Injury in a Rat Model
Authors: Jude Morgan Blair , Izadi Ali , Shahlaie Kiarash , Gurkoff Gene G.
Published: March 2023

INTRODUCTION:

Traumatic brain injury (TBI) is a major source of morbidity and mortality worldwide. In previous studies, intravenous ziconotide, a selective N-type voltage-gated calcium channel blocker, reduced brain calcium accumulation, improved brain mitochondrial respiration, and improved cognitive and motor outcomes in rodent models of TBI. Attempts to translate intravenous ziconotide therapy to humans were halted due to peripheral side-effects. However, ziconotide is now FDA-approved for treatment of severe pain syndromes when administered intrathecally instead of intravenously. We hypothesize that following TBI intraventricular ziconotide will improve cognitive function in the absence of significant side effects.

METHODS:

Seventy-seven Sprague-Dawley rats underwent sham (n = 11 males, n = 11 females) or lateral fluid percussion (LFP) injury (n = 21 males, n = 23 females). One-hour post-injury, rats received either an intraventricular injection of saline (n = 22 sham, n = 23 LFP) or ziconotide (n = 21 LFP). A catheter was implanted in the left lateral ventricle and connected to an Alzet micro-osmotic pump to allow for 72 hours of continuous infusion. Cognitive outcomes were evaluated using Morris water maze (MWM; days 10-15).

RESULTS:

TBI-saline rats performed significantly worse than shams on MWM (p < 0.01). Ziconotide treated rats had an intermediate phenotype on MWM. TBI-saline rats swam a less efficient path than sham animals (p < 0.01); ziconotide path efficiency was not significantly different from shams. Performance on the MWM was likely not related to motor deficits as there was no significant effect of group on mean swimming speed in either males or females. Female sham animals performed significantly better on probe trials compared to TBI-saline (p < 0.05); ziconotide animals were not different from shams.

CONCLUSIONS:

These findings support centrally delivered Ziconotide as a potential neuroprotective agent to improve cognitive performance following TBI. Further studies are required to characterize the neuroprotective effects of Ziconotide therapy.
347 Management of Rathke Cleft Cysts in Children: The Rady Children’s Hospital Approach
Authors: Brandel Michael G. , Plonsker Jillian Hannah , Rennert Robert , Khan Usman , Nation Javan , Crawford John R. , Levy Michael L.
Published: March 2023

INTRODUCTION:

Rathke cleft cysts (RCCs) are benign, epithelial-lined sellar lesions that arise from remnants of the craniopharyngeal duct. Due to their rarity in the pediatric population, data are limited regarding the natural history and management of growing or symptomatic RCCs.

METHODS:

We performed a retrospective study of RCC patients age ≤18 years treated between 2006-2022 at our institution.

RESULTS:

567 patients with a diagnosis of pituitary mass or cyst were identified. Of these, 31 underwent surgery and had a histopathological diagnosis of RCC, 58% female and 42% male. Mean age was 13.2 +/- 4.2 years. Presenting symptoms included headache (58%), visual changes (35%), and endocrinopathies or growth delay (26%); 13% were identified incidentally and grew significantly on serial imaging. Six percent presented with intralesional hemorrhage. Surgical approach was transsphenoidal for 90% of patients and orbitozygomatic for 10%. Preoperative headaches resolved in 61% of patients after surgery. New pituitary axis deficits were seen in 9.7%. Only two complications occurred from a first-time surgery: one cerebrospinal fluid leak requiring lumbar drain placement, and one case of epistaxis requiring cauterization. No patients experienced new visual or neurological deficits. Patients were followed postoperatively with serial imaging. Mean follow-up was 62.9 +/- 58.4 months. Recurrence requiring reoperation occurred in 32% of patients (transsphenoidal n = 8, pterional n = 2). Five-year progression-free survival was 47.9%. Except for one patient with multiple neurological deficits from a concurrent tectal glioma, all patients had a modified Rankin Scale score of 0 or 1 (good outcome) at last follow-up.

CONCLUSIONS:

Due to their secretory epithelium, RCCs may demonstrate rapid growth and recurrence. Incidental RCCs can be managed conservatively, whereas symptomatic or growing lesions may be fenestrated or resected. Due to their dynamic and variable nature, careful patient selection and close postoperative surveillance are critical to optimizing patient outcomes.
351 Claudin 6 Expression in Atypical Teratoid/Rhabdoid Tumors is a Target for CAR-T Cell Therapy
Authors: Madsen Peter J. , Stern Allison , Griffin Crystal , Oehm Petr , Rengstl Benjamin , Flemmig Carina , Tucker Alexander , Storm Phillip B. , Resnick Adam C. , Foster Jessica
Published: March 2023

INTRODUCTION:

Novel therapies for atypical teratoid/rhabdoid tumor (ATRT) are desperately needed. Claudin-6 (CLDN6) is a tight junction protein present during early development and in some tumors, but not at appreciable levels in normal tissue. CLDN6-targeted chimeric antigen receptor (CAR) T cells with a CAR-T cell–amplifying RNA vaccine have demonstrated antitumor activity against CLDN6-expressing cancers in pre-clinical and clinical trials (NCT04503278; Haanen J et al AACR, 2022).

METHODS:

CLDN6 expression was assessed on primary ATRT specimens by RNAseq and immunohistochemistry and on tumor-derived cell lines by flow cytometry. CLDN6-positive and negative cell lines were co-cultured with CLDN6-targeting CAR-T cells and killing efficacy was measured. A second-generation mRNA CAR with a 4-1BB costimulatory domain and single-chain variable fragment directed against CLDN6 was used (Reinhard et al, 2020). Cell lines were modified with reporter assays and intracranial xenografts were created in NSG mice.

RESULTS:

50% of specimens had CLDN6 expression greater than 2 FPKM (N = 28). Immunohistochemistry was positive in 53% of specimens (N = 15). Multiple CLDN6-positive ATRT cell lines were identified by flow cytometry. Co-culture of CLDN6-directed mRNA CAR-T cells with ATRT line 7316-2187 resulted in tumor-specific cytotoxicity versus CD19-directed control CAR-T cells (92% versus 15% at 10:1, p < 0.0001; 86% versus 0% at 5:1, p < 0.0001). Similar results were seen with an additional CLDN6-positive ATRT cell line 7316-2141 (75% versus 7% at 10:1, p < 0.0001; 53% versus 0% at 5:1, p < 0.0001). Both CLDN6- and CD19-directed CAR-T cells showed no cytotoxicity against a CLDN6-negative cell line, 7316-4149. Xenografts were successfully created, and ongoing work is evaluating locoregional administration of CLDN6-directed CAR-T cells.

CONCLUSIONS:

This work highlights the potential of targeting CLDN6 with CAR-T cell therapy as a novel treatment strategy for patients with ATRT.
353 Cerebellar Tonsil Reduction for Surgical Treatment of Chiari I Malformation in Children
Authors: Montgomery Eric , Swift Dale , Pernik Mark Nicholas , Whittemore Brett A. , Weprin Bradley , Price Angela V. , de Oliveira Sillero Rafael , Braga Bruno
Published: March 2023

INTRODUCTION:

There remains much debate around ideal surgical technique for Chiari Malformation Type 1. Although recent trends favor less invasive techniques, growing evidence may support tonsillar reduction via resection or coagulation.

METHODS:

We retrospectively reviewed 456 consecutive children (<18 years of age) surgically treated for Chiari I malformation. Procedures were classified into four groups: bone decompression (PFD) and duraplasty (PFDD), PFDD with arachnoid dissection (PFDD + AD), PFDD with coagulation of at least one cerebellar tonsil (PFDD + TC) and PFDD with subpial resection of at least one tonsil (PFDD + TR).

RESULTS:

Preoperatively, univariate analysis showed that brainstem/spinal cord symptoms, use of cine MRI, tonsil length, and distance from the opisthion to brainstem were correlated with the surgical technique used. Multivariate analysis demonstrated that only tonsil length was independently associated with surgical technique choice: it was directly associated with utilization of PFDD + TR over PFDD (p = 0.001) or PFDD + AD (p = 0.005) and with PFDD + TC over PFDD (p = 0.005). Postoperatively, symptoms improved in 56/71 (78.9%) of patients in the PFDD group, 23/26 (88.5%) in PFDD + AD, 77/92 (83.7%) in PFDD + TC and 235/267 (88.0%) in PFDD + TR. Syringomyelia improved greater than 50% in 80.4% of patients in PFDD + TC/TR versus only 58.8% of PFDD + D/AD (p = 0.001). Reoperation rates and postoperative headaches were decreased (3.1% and 14.5%, respectively) in the PFDD + TC/TR group compared to the PFDD + D/AD group (8.3% and 25.8%, respectively), and they were both statistically significant (p-value = 0.023 and 0.008, respectively). Postoperative complication rates were not statistically different between the groups.

CONCLUSIONS:

In this single center retrospective series, cerebellar tonsil reduction, by either coagulation or sub-pial resection, results in superior reduction of syringomyelia in Chiari I patients with less reoperations and without increased complications.