bluuebunny/crossref_metadata_2025 huggingface dataset:
249 Interprofessional Consultation to Reduce Unnecessary Transfers of Complicated Mild TBI to Tertiary Referral Centers
Authors: Blitz Sarah , Rosen Carlo , Anderson Jonathan , Stenson Bryan , Stippler Martina
Published: March 2024

INTRODUCTION:

The neurosurgical intervention rate for complicated mild traumatic brain injury (cmTBI) is less than 1%. However, the absence of transfer guidelines and fear of malpractice results in unnecessary transfers of cmTBI patients to tertiary referral centers.

METHODS:

Between April 2021 and March 2023, we implemented a Tele-TBI at three community hospitals for cmTBI patients seen in the emergency department (ED). An interprofessional telehealth-based consultation between emergency medicine and neurosurgery determined if a patient needed to be transferred to the Level-1Trauma Center or could be cared for at the community hospital. A retrospectively chart review was used to determine if transfers were unnecessary. Transfer rates were compared for patients from hospitals with and without the Tele-TBI protocol.

RESULTS:

Out of 822 cmTBI patients seen in our ED, 73% (n = 602) were transferred from other hospitals. The mean age of transferred patients was 67.5 (±19.9) and median GCS was 15. During this time, 128 Tele-TBI consultations were performed. The mean age was 75.7 (±16.2), and median GCS was 15. The overall transfer rate was decreased by 89% (n = 15/128) when Tele-TBI consultations were initiated. Tele-TBI-enabled hospitals had significantly fewer (p < 0.001) unindicated transfers (28.7%, n = 66 versus 71.3% n = 164) and led to fewer (p = 0.003) transferred patients discharged directly from the Level-1Trauma Center ED (28.6%, n = 66 versus 72.3%, n = 173). ICU admissions and frequency of neurosurgical intervention did not differ between hospitals with or without tele-TBI implementation.

CONCLUSIONS:

Interprofessional telehealth-based consultation can effectively triage patients with cmTBI presenting to community hospitals, leading to fewer unnecessary transfers with similar rates of ICU admissions and neurosurgical interventions.
261 Perioperative Complications and Secondary Retethering After Pediatric Tethered Cord Release Surgery
Authors: Pan James , Boop Scott , Barber Jason , Susarla Srinivas , Durfy Sharon , Ojemann Jeffrey G. , Goldstein Hannah Emily , Lee Amy , Browd Samuel R. , Ellenbogen Richard G. , Hauptman Jason Scott
Published: March 2024

INTRODUCTION:

Tethered cord syndrome refers to a constellation of symptoms characterized by neurological, musculoskeletal, and urinary symptoms, caused by traction on the spinal cord. Various surgical techniques have been developed to address tethered cord syndrome depending on a diverse set of etiologies. Understanding perioperative complications and secondary retethering is crucial for optimizing patient outcomes and refining surgical techniques.

METHODS:

Retrospective review of children who underwent TCR surgery from July 2014 to April 2023. Data included demographics, perioperative characteristics, surgical techniques, and follow-up duration. Primary outcomes were 60-day postoperative complications and secondary retethering requiring repeat surgery.

RESULTS:

We identified 363 TCR surgeries (145 simple, 218 complex, 340 subjects). Mean follow-up was 446 days for simple TCRs and 731 days for complex TCRs. The adjusted 60-day complication rate was 3.8% (95%-CI 1.6-9.1) for simple TCRs and 11.9% (95%-CI 9.0-19.4) for complex TCRs. Lower weight, shorter surgical times, and ICU admission were associated with complications for simple TCRs. Soft tissue drains increased complications for complex TCRs. Secondary retethering rates were 1.4% for simple TCRs and 11.9% for complex TCRs. The 1-, 3-, and 5-year progression-free survival in complex cases were 94.7% (95%-CI 89.1-97.4), 77.7% (95%-CI 67.3-85.3), and 62.6% (95%-CI 46.5-75.1). Multivariate analysis revealed that prior detethering (OR 8.15, 95%-CI 2.33-28.50, p = 0.001) and usage of the operative laser (OR 10.43, 95%-CI 1.36-80.26, p = 0.024) were independently associated with secondary retethering in complex cases.

CONCLUSIONS:

This is the largest series examining postoperative complications and long-term secondary retethering in TCR surgery. Simple TCR surgeries demonstrated safety, rare complications, and low secondary retethering rates. Complex TCR surgeries presented higher risks for complications and secondary retethering. Modifiable risk factors, such as operative laser usage, influenced secondary retethering in complex cases.
270 Inducing Neural Maturation and Increasing Survival in SHH Medulloblastoma Using EZH2 Inhibition in a Mouse Model
Authors: Orillac Cordelia Marcela , Snuderl Matija , Galbraith Kristyn , Tylawsky Daniel , Liechty Benjamin , Vaynshteyn Jake , Gerwin Jeffrey , Boue Daniel , Heller Daniel , Raju Praveen
Published: March 2024

INTRODUCTION:

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Genetically, MB can be divided into four subgroups of which the SHH subtype histologically shows nodular architecture. Within this nodular architecture, there are islands of mature cells, with more abundant neuropil and a low proliferation rate, scattered among sheets of primitive cells.

METHODS:

We performed laser capture microdissection followed by whole transcriptome analysis, spatial transcriptomics using Digital Spatial Profiling, whole genome DNA methylation and ChIP-Seq analysis of mature and primitive areas from 8 medulloblastomas. We developed a genetically-engineered mouse model of SHH MB showing spontaneous maturation and lack of maturation with a conditional EZH2 genetic ablation or EZH2 overactivation respectively. Finally, we developed a fucoidan-based nanoparticle drug delivery across the blood brain barrier (BBB) for targeted molecular inhibition.

RESULTS:

Using whole transcriptome and DNA methylation analysis, we identified ∼120 differentially expressed genes between primitive and mature regions with enrichment for genes regulated by H3K4me3 and H3K27me3. ChIP-Seq analysis showed striking differences in H3K27me3 enrichment between primitive and mature medulloblastoma cells including at the EZH2 locus. Medulloblastoma specific EZH2 genetic ablation resulted in diffuse tumor cell differentiation and prolonged survival in mice (n = 10 per group, log-rank p = 0.01). Conversely, conditional EZH2 (Y641F) activation prevented medulloblastoma differentiation. A fucoidan-based nanoparticle successfully delivered the EZH2 inhibitor (EPZ-6438) across the murine BBB to achieve significant extension of mouse survival (median 70 days compared to 21 days in control mice; *p = 0.01, Mantel-Cox).

CONCLUSIONS:

Spontaneous maturation of medulloblastoma cells can be induced by inhibition of EZH2. Fucoidan-based nanoparticle delivery systems allows tumor specific targeted delivery across the BBB extending survival in mice.
272 Integrative Genomics Implicates Primary Impact on Cortical Development in Spina Bifida
Authors: Phan Duy , Shaffrey Mark Edwin , Park Min S.
Published: March 2024

INTRODUCTION:

Spina bifida is one of the most common malformation of the central nervous system that is associated with poor neurodevelopmental outcomes. Altered neurodevelopment in spina bifida has been attributed to venting of CSF through the neural tube defect. Despite correction of the spinal defect, some patients still develop hydrocephalus with poor neurodevelopmental outcomes, suggesting incomplete understanding of disease pathogenesis. Recent human genetic efforts have identified candidate genes that confer spina bifida risk, however, the mechanisms linking gene mutations to altered neurodevelopment remain poorly understood.

METHODS:

We curated a list of 439 genes that confer risk to spina bifida from a whole-genome sequencing study of 310 individuals. We then mapped the spatiotemporal and cell-type specific expression of these risk genes onto bulk and single-cell RNA sequencing data of normally developing human brains covering the entire lifespan of human development.

RESULTS:

We found that spina bifida risk genes are enriched at post-conception weeks 5-6 and 25-38 in the developing human brain. After birth, spina bifida risk genes are enriched at postnatal months 6-10 and then after 60 years of age. At the cell type level, spina bifida risk genes are enriched in proliferative neuroprogenitor cells and microglia in the prenatal human cortex.

CONCLUSIONS:

Our analyses show that spina bifida risk genes are expressed in the developing human brain, suggesting a primary impact on brain development that is independent from the open caudal end of the neural tube defect. The finding that spina bifida risk genes continue to be expressed postnatally suggests a window for therapeutic intervention to optimize neurodevelopmental outcomes after birth in at least a subset of patients.
290 A Rib-Sparing Unilateral Transpedicular Thoracic Corpectomy Using the Ultrasonic Bone Scalpel: A Novel Technique and Pictorial Guide
Authors: Foster Chase H. , Mehta Aadit Piyush , Floyd Calvin , Herzig David Warren , Levine Zachary , Rhee Jay W.
Published: March 2024

INTRODUCTION:

Posterior thoracic corpectomies typically require removal of the costotransverse articulation and some amount of the adjoining rib, an accompaniment that has been shown to result in significant post-operative morbidity. There are several well-described approaches to pathology of the thoracic spine, each with advantages, disadvantages, and inherent limitations.

METHODS:

The technique is demonstrated step-by-step in a videographic pictorial description of the procedure performed on both a molded plastic spine model and on a cadaveric specimen. A retrospective chart review was conducted on patients having undergone this thoracic corpectomy technique since its implementation at the senior author’s institution. Patient data, operative metrics, and outcomes were collected and analyzed.

RESULTS:

A total of 36 corpectomies were performed on 32 patients (mean age = 63 years). There were oncological (n = 22, 69%), degenerative/traumatic (n = 7, 22%), and infection (n = 3, 9%) indications. EBL averaged 853 cc for 30/32 cases. Operative time averaged 177.83 minutes. Length of stay averaged 6.47 days. One clinically inconsequential iatrogenic durotomy occurred. One patient had a surgical site infection three weeks later that required wound washout without hardware revision.

CONCLUSIONS:

Rib resection correlates with significant post-operative pain. This thoracic corpectomy technique mitigates morbidity by avoiding manipulation, destabilization, or resection of the rib, potentially permitting faster recovery and discharge. The technique is dependent on the UBS as it expediently creates a tailored window for an expandable corpectomy cage. A rib-sparing thoracic corpectomy can be effectively, efficiently, and safely performed using a combination of the UBS and an expandable cage during a single stage posterior-only unilateral transpedicular approach with which most spine surgeons are familiar.
295 High Volume Centers Provide Superior Value of Care in the Surgical Treatment of Malignant Brain Tumor
Authors: Vazquez Sima , Dominguez Jose Fernando , Spirollari Eris , Soldozy Sauson , Ivan Michael E. , Merenzon Martin Andres , Hanft Simon Jeremy , Komotar Ricardo Jorge
Published: March 2024

INTRODUCTION:

Improved outcomes in surgical patients have been associated with increasing volume of cases. This has led to the development of centers that facilitate care for a specific patient population.

METHODS:

The 2016-2020 National Inpatient Sample (NIS) was queried for patients undergoing resection of malignant brain tumors. Teaching hospitals with high case load (greater than two standrad deviations above the mean, or >140 cases) were categorized as high-volume centers (HVC). Value of care was computed by adding one point for each of the following variables: lower length of stay, lower total charges, discharge to home, and lack of major comorbidity or complication, as defined per DRG codes.

RESULTS:

A total of 118,390 patients underwent resection of malignant brain tumors in 3,009 hospitals. HVC criteria was met by 91 (3%) hospitals, which represented 20,230 (17.1%) of total cases. The Mid-Atlantic and South Atlantic regions had the highest percentage of cases (22.7% and 20.2%, respectively) and number of HVC (21 and 17, respectively). Value of care was higher at HVC (OR = 1.35 95%CI 1.31-1.39 p < 0.01). After controlling for baseline risk factors and high risk admissions, HVC was associated with decreased complications of intracranial hemorrhage, deep venous thrombosis, aspiration pneumonitis, acute kidney injury, and external ventricular drain requirement (p < 0.01 for all). HVC was also associated with decreased length of stay and increased rate of discharge to home (p < 0.01 for both).

CONCLUSIONS:

Patients undergoing craniotomy for malignant brain neoplasms have superior outcomes in HVC. Trends of centralization are likely a reflection of the benefits of multidisciplinary treatment for these patients. Improvement of access to care at these institutions may improve the efficiency of the delivery of care for these patients.
297 Impact of Navigated Intraoperative Ultrasound on Brain Shift and Gross Tumor Resection
Authors: West Timothy , Mazurek Mercy H. , Razak Shahaan S. , Gal Zsombor Tamas , Perez Nicole , Burrows Akeive , Choi Bryan D. , Nahed Brian V.
Published: March 2024

INTRODUCTION:

Intraoperative imaging and neuronavigation aid in achieving maximum tumor resection. However, tissue removal during surgery can cause brain shift, which alters the relative anatomy and “de-calibrates” the standard approaches. While intraoperative MRI (iMRI) is the gold-standard to correct for brain shift, it is expensive, time-consuming, and logistically difficult. As an alternative, we investigated an approach which combines intraoperative ultrasound (ioUS) technology with preoperative imaging to allow for real-time compensation of brain shift and assessment of extent of resection (EOR).

METHODS:

We prospectively enrolled patients undergoing neurosurgical tumor resection at Massachusetts General Hospital beginning April 2023. Patients were registered with Brainlab Ultrasound Navigation prior to surgery. ioUS sweeps were acquired before cortex incision, mid-resection, and post-resection with bkActiv and fused to preoperative MRIs. Four points around the tumor were longitudinally tracked to assess brain shift. Data included sweep duration, image processing speed, extent of brain shift as determined by intraoperative markers, and EOR assessed from the ioUS compared with postoperative MRIs.

RESULTS:

Seven patients were enrolled (average age 62 ± 15, 75% male) with frontal (n = 5), temporal (n = 1), and occipital (n = 1) gliomas (n = 4) and metastases (n = 3). All patients exhibiting total resection as determined by ioUS also demonstrated total resection on post-operative MRI, evaluated independently by a neuroradiologist. The average time of scan and image processing (n = 19) was 5.7 ± 1.9 and 27.8 ± 6.5 seconds respectively.

CONCLUSIONS:

Navigated ioUS offers accurate and efficient assessment of EOR during surgery for tumor resections. Furthermore, when brain shift is detected, navigated ioUS can allow for compensation and continued utilization of navigation via the acquisition of a brand new, navigable, intraoperatively acquired dataset.
300 Intracranial Tumors Hijack the Meningeal Venolymphatic Network Through VEGFR-2 Signaling
Authors: Ampie Leonel , McGavern D.
Published: March 2024

INTRODUCTION:

Glioblastoma and other intracranial neoplasms have been associated with breakdown of the blood brain barrier. Other protective CNS barriers have sparsely been studied in brain tumors. Here, we identify the ability of intracranial neoplasms to hijack the meningeal venolymphatic network, which is driven through VEGFR-2/VEGF-A signaling.

METHODS:

C57BL/6J mice were stereotactically injected with syngeneic SB28 (glioblastoma) cell lines. Mice were treated with either isotype control or a VEGFR-2 inhibitor. Two-photon microscopy was used to visualize vascular cytoarchitecture and dynamics in vivo. Meningeal whole mounts, brains and spleens were also collected and analyzed by confocal microscopy and high parameter flow cytometry. Human dura mater from glioblastoma patients underwent multiplex immunohistochemistry to confirm the translatability of our findings.

RESULTS:

Our imaging studies revealed that glioblastomas can generate an extensive de novo network of meningeal blood vessels and lymphatics both in mice and humans. Lymphatic vessels were often observed developing in parallel to the newly formed vasculature. Intravital two-photon microscopy further revealed that the peritumoral vascular bed in the meninges of mice was leaky, dysfunctional, and generated a hypoxic microenvironment. Importantly, inhibition of VEGFR signaling impeded formation of this faulty venolymphatic network, which slowed tumor growth, reduced peritumoral hypoxia, enhanced immune infiltration, and increased survival.

CONCLUSIONS:

Our results demonstrate that glioblastomas can invade the meninges and hijack the venolymphatic network through VEGFR-2 and PECAM-1 signaling. While VEGFR-2 is associated with angiogenesis, our data suggest that it may also have an important role in regulating the simultaneous development of de novo meningeal venous and lymphatic drainage during glioblastoma.
303 Long-Term Volumetric Analysis of Non-functioning Pituitary Microadenomas: An International, Multi-center Cohort Study
Authors: Kilgallon John , Sarkar Sauradeep , Omara Chady , Sajed Sulaiman , Bakker Leontine , Biermasz Nienke , Van Furth Wouter Ralph , Verstegen Marco , Lobatto Daniel , Drexler Richard , Flitsch Jörg , Ricklefs Franz Lennard , Ryba Alice , Guaraldi Federica , Smith Timothy R. , Min Le
Published: March 2024

INTRODUCTION:

The incidental finding of pituitary microadenomas (PmAs) is increasingly common due to the widespread use of MRI. To date, no comprehensive volumetric analyses of PmAs growth patterns have been conducted. A greater understanding of how these lesions progress could influence an array of management strategies, including frequency of imaging and the use of surgical versus conservative medical intervention.

METHODS:

Patients who underwent = 2 pituitary MRIs for suspected PmAs were identified retrospectively across 4 referral centers worldwide. Patient demographics, presenting symptoms, clinical variables, MRIs, and treatment course were collected and analyzed.

RESULTS:

A total of 447 patients (Male = 126; 28.2%) referred to the 4 centers from 2003 to 2022 were identified. Median age at first MRI was 43 years [IQR 32–54]. Median number of MRIs per patient was 3 [IQR 2–5] and median follow-up time was 55 months [IQR 29–100]. 300 PmAs (67.1%) were solid, 102 (22.8%) were cystic, 47 (10.5%) were uncertain, and 24 (5.4%) were mixed. At baseline, median suspected tumor volume was 45 mm3 [15–103]. 77 patients (17.2%) presented with subclinical hyperpituitarism, most often hyperprolactinemia, while 67 (15.0%) experienced hypopituitarism such as hypogonadism, hypothyroidism, and growth hormone deficiency. During follow-up, new onset hyperpituitarism was detected in 20 patients (4.5%) along with hypopituitarism in 9 (2.0%). During the study period, 225 patients (50.3%) had no change in suspected PmA growth, 144 (32.2%) had a decreased size, and 101 (22.6%) had an increased size. 80 patients (17.9%) received medical therapy and 48 (10.7%) underwent transsphenoidal surgery.

CONCLUSIONS:

With the forthcoming volumetric analysis, we hope to gain further insights into predictors of long-term volumetric evolution of PmAs to improve patient management.
332 Descriptive Analysis of State and Federal Malpractice Litigation in the United States Related to Neuroendovascular Procedures
Authors: Amjadi Nazaneen , Desai Sohum
Published: March 2024

INTRODUCTION:

Medical malpractice interests the medical community at large. While previous neurosurgical review articles have analyzed malpractice in the context of spinal surgery, few have reviewed malpractice data surrounding neurovascular procedures as a whole.

METHODS:

In this retrospective review Google Scholar Case Law, Casetext and Westlaw legal databases were searched for verdict and settlement reports pertaining to neurovascular procedures from 1984 to 2023. Data were collected regarding type of procedure, patient age and gender, defendant specialty, outcome, award, and alleged cause of malpractice. Search terms included “arteriovenous malformation,” “brain aneurysm,” “aneurysm coiling,” “subarachnoid hemorrhage,” “large vessel occlusion,” “mechanical thrombectomy,” “cerebral angiography,” “carotid angioplasty and stenting,” and “carotid stenosis.” Initial search produced 212 cases, after which exclusion criteria were applied to eliminate duplicates and cases unrelated to neurovascular surgery/diagnoses or malpractice, yielding 27 cases total.

RESULTS:

The verdict favored the defendant physician(s) individually or represented by a healthcare entity in 8 of the 27 cases selected for analysis. Of 19 cases with verdicts in favor of the plaintiff, settlement values ranged from $30,000 to $15.65 million. In settlement cases, the most commonly involved procedures included AVM embolization followed by aneurysm coiling. Amongst cases where interventionist was the defendant, the most common specialty was neurointerventional radiology, followed by neurosurgery. Failure to diagnose was the most cited alleged malpractice cause (51.8%) amongst all cases, regardless of verdict.

CONCLUSIONS:

Neurovascular emergencies are often addressed by a team of medical specialists including endovascular neurosurgeons, interventional neuroradiologists, and interventional neurologists. In this review, malpractice claims related to neurovascular emergencies most likely to result in plaintiff award were related to failure to diagnose, and interventional neuroradiologists appear to be at greater risk for alleged malpractice.
385 Genomic Alterations Associated With Postoperative Nodular Leptomeningeal Disease After Resection of Brain Metastases
Authors: Morshed Ramin , Cummins Daniel Dighton , Nguyen Minh P. , Saggi Satvir , Vasudevan Harish , Braunstein Steve , Goldschmidt Ezequiel , Chang Edward F. , McDermott Michael William , Berger Mitchel S. , Theodosopoulos Philip V. , Daras Mariza , Hervey-Jumper Shawn L. , Aghi Manish Kumar
Published: March 2024

INTRODUCTION:

The relationship between brain metastasis resection and risk of nodular leptomeningeal disease (nLMD) is unclear. Prior studies have not explored genomic alterations associated with postoperative nLMD.

METHODS:

A retrospective, single-center study was conducted with patients who underwent resection of a BM with available clinical and genomic data available. Postoperative nLMD was the primary endpoint of interest. Targeted next-generation sequencing of over 500 oncogenes using a CLIA certified assay was performed in brain metastases. Cox proportional hazards analyses were performed to identify clinical features and genomic alterations associated with nLMD.

RESULTS:

One hundred and one patients composed the cohort with tumors originating from multiple cancer types. There were 15 cases of nLMD (14.9% of the cohort) with a median time from surgery to nLMD diagnosis of 8.2 months. Two supervised machine learning algorithms consistently identified CDKN2A/B co-deletion and ERBB2 amplification as the top predictors associated with postoperative nLMD across all cancer types. In a multivariate Cox proportional hazard analysis including clinical factors and genomic alterations observed in the cohort, tumor volume (HR 8.8, 95% CI 1.1-69, p = 0.04), CDKN2A/B co-deletion (HR 5.3, 95% CI 1.7-16.9, p = 0.004), and ERBB2 amplification (HR 3.9, 95% CI 1.1-14.4, p = 0.04) were associated with decreased time to postoperative nLMD.

CONCLUSIONS:

In addition to increased resected tumor volume, ERBB2 amplification and CDKN2A/B deletion were independently associated with an increased risk of postoperative nLMD across multiple cancer types. Additional work is needed to determine if targeted therapy decreases this risk in the postoperative setting.
414 Exploration and Validation of CSF miRNAs as Predictors of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Prospective Clinical Study
Authors: Blackburn Spiros L. , Ali Shafeeque Mohammed , Mcbride Devin , Zeineddine Hussein A , Thankamanipandit Peeyush
Published: March 2024

INTRODUCTION:

Approximately one-third of the patients who survive Aneurysmal Subrachnoid Hemorrhage (aSAH) have delayed cerebral ischemia (DCI) which contributes to poor clinical outcome.

METHODS:

A prospectively maintained clinical database was utilized under IRB approval for determination of clinical DCI and collection of biological samples. CSF samples were collected at 2-time points (<24 hours and 72 hours) post-aSAH from patients treated with external ventricular drainage. miRNAs were extracted from exosomes isolated from the CSF. In the first group of patients (exploratory phase), a CSF panel containing 84 miRNAs was analyzed using quantitative real-time PCR as an exploratory phase. Using the findings from the exploratory phase, we subsequently validated 26miRNAs in a second group of patients.

RESULTS:

We found three miRNAs i.e., miR-150-5p (p=0.02), miR-140-3p (p=0.03), and miR-26b-5p (p=0.01) were significantly upregulated in 72 vs 24 hours in patients that developed DCI. Moreover, we observed miR-451a (p=<0.0001) and miR-106a-5p (p=0.0001) were upregulated in No DCI at 72 hours.

CONCLUSIONS:

Our study identifies CSF exosomal miRNAs that could be crucial in progressing aSAH to DCI, and another set of miRNAs that possibly helps in aiding protection being entered into DCI. These miRNAs could be considered as potential biomarkers for DCI progression and prevention. Specifically miR-451a and miR-106a-5p may provide a protective role by reducing inflammation mediated by Matrix Metalloproteinases genes, thus crucial in the prevention of DCI. Further validation is important in additional patient cohorts.
415 Cryopreserved Human Umbilical Cord in the Treatment of Pediatric Tethered Cord Syndrome
Authors: Kiehna Erin Nicole
Published: March 2024

INTRODUCTION:

Tethered cord syndrome (TCS) is characterized by neurological, gastrointestinal/genitourinary, and musculoskeletal dysfunction attributable to spinal cord traction. It is estimated that 20-50% of children with open and closed neural tube defects repaired after birth will require surgery to detether the spinal cord. The cryopreserved human umbilical cord (HUC) patch has regenerative, anti-inflammatory, and anti-scarring properties. In animal models, when HUC is used as a meningeal patch it allows regeneration of the arachnoid layer, prevents spinal cord tethering, and improves spinal cord function after in utero spina bifida repair. We hypothesized that this would benefit pediatric patients requiring detethering.

METHODS:

Serial patients with clinical and radiographic evidence of a tethered cord were enrolled following informed consent. At the time of surgery they underwent spinal cord detethering with neuromonitoring. At the time of closure a HUC graft (Clarix 1k) was placed as a dural underlay, the dura was closed primarily, and a second graft was placed as a dural overlay and sealed with tissue sealant. Serial neurologic assessments and urologic assessments were obtained. MRIs are performed annually or as indicated clinically.

RESULTS:

Four patients have been detethered with use of HUC as a dural underlay and overlay (2 lipomyelomeningocele, 1 lipoma/diastematomyelia, 1 tethered cord). One patient remains neurointact, with resolution of mild neurogenic bladder. Another patient has gained sensation of lower extremities, sensation to catheterization, with resolution of neurogenic bowel and bladder. One has gained sensation to catheterization, with resolution of neurogenic bowel and bladder. The fourth patient is stable.

CONCLUSIONS:

Early use of HUC as a dural underlay and overlay during closure for tethered cord surgery shows promise in improving spinal cord function in pediatric patients.
448 Motor Control of Bladder Function by Nerve Transfer
Authors: Johnston Benjamin , Brown Justin M. , De Elise , Ruggieri Michael , Lemos Nucelio , McGovern Francis
Published: March 2024

INTRODUCTION:

A normal detrusor muscle is activated by parasympathetic efferents that release acetylcholine to muscarinic receptors to contract and expel urine. Through canine work by our group, the scientific underpinning of a somatic nerve transfer to a visceral target (hybrid synapse) was established. We present the scientific basis of this hybrid nerve transfer and report the first-in-human functional outcome.

METHODS:

Our patient presented with deteriorating bladder function over 1 year and underwent en bloc resection of a sacral chondrosarcoma in December 2020. The sacral roots from S1 caudally were divided – resulting in loss of bowel and bladder function. Urodynamics demonstrated an acontractile bladder (0 cm H20). In May 2021 bilateral obturator nerve transfers to the vesical branches (to bladder) of the inferior hypogastric plexus (6 months after surgery). Patient bladder function and pelvic visceral sensation were followed with serial urodynamic studies.

RESULTS:

The patient was asked to adduct the thighs and relax the abdomen to initiate a detrusor (bladder) contraction. This provided definitive activation of the nerve transfer in November 2022 (1.5 years after transfer), which was confirmed in January 2023 (∼20 cm H20). Concomitantly, the filling volume at which “full bladder” was perceived appeared at 6 months and progressed until detected within normal range of bladder volumes.

CONCLUSIONS:

This is a first-in-human nerve transfer that has clear evidence of visceral sensation recovery (need to void) at normal volumes, and functional detrusor contraction. While bladder pressures produced were not within normal range, we expect transfers earlier after loss of function (e.g. within 6 months instead of 18) will result in greater functional gains.
454 Utilization of Adipose-Derived Stem Cells in Cranial Nerve Regeneration: A Systematic Review
Authors: Aguirre Alexander Otilio , Chee Keanu , Harris Mark , Himstead Alexander Scott , Dzihich Ermin , Brown Nolan James , Musmar Basel , Kuo Cathleen , Bui Nicholas , Kortz Michael
Published: March 2024

INTRODUCTION:

Large peripheral nerve injuries may require surgical reconnection. Cell-based therapies have also been investigated for nerve regeneration.

METHODS:

PubMed and Embase databases were used to search for primary studies reporting the use ADSCs in the regeneration of cranial nerves. A total of 12 studies were included which all presented data on specific neural injury, therapy, and functional outcomes.

RESULTS:

Eight studies focused on the facial nerve (66.7%), two on the optic nerve (16.7%), one on the olfactory nerve (8.3%), and one on the hypoglossal nerve (8.3%). One study applied ADSCs to human cranial nerve injuries, while the remainder studied animal models. In these studies, ADSC groups had higher numbers of myelinated fibers, increased myelin thickness and diameter of muscle fibers as well as greater magnitude of compound muscle action potentials (CMAP) when compared to controls. In studies focused on optic nerve regeneration, significant improvements across visual tests were observed.

CONCLUSIONS:

ADSCs demonstrate potential utility in regard to their ability to facilitate functional recovery of cranial nerves in humans as well as animal models. Further investigation into the use of ADSC should be pursued in both animal and early human studies to validate the findingsof previous literature.
457 Timing of Surgery as an Outcome Predictor in Brachial Plexus Injury: A Systematic Review and Meta-Analysis
Authors: Hanna Amgad , Moscote-Salazar Luis Rafael , Florez-Perdomo William , Moriones Natalia Guevara
Published: March 2024

INTRODUCTION:

Injuries that affect the brachial plexus are considered to have a high impact on the quality of life of patients. Brachial plexus injuries in adults require reconstruction using microsurgical techniques. At least, there is still controversy about the impact of the timing of surgical reconstruction and its effect on outcome.

METHODS:

We searched PubMed, EMBASE, Cochrane Library, SCOPUS, and MEDLINE, up to March 2023, for published studies on evidence of timing of surgery in Brachial plexus injury and neurological outcome. Primary outcome Good motor functional Recovery (MRC).

RESULTS:

In this meta-analysis, it was found that early surgical treatment before 6 months post-injury increases motor recovery (MRC) three times more than late intervention (after 6 months) with adequate statistical significance and good homogeneity (OR 3,115 [95% CI 2,248–4,317] p = <0.0001; I2 = <0.00001%).

CONCLUSIONS:

The available evidence suggests that performing brachial plexus surgery in less than 6 months can be associated with a better outcome. Further research is needed to characterize various subgroups of BPI patients. It is necessary to improve the quality of the evidence, so we suggest the creation of a multicenter database in the United States that allows us to obtain better conclusions.
462 Stem Cell-Loaded Implantable Intrathecal Bioreactors for the Treatment of Spinal Cord Injury: A Porcine Model Pilot Study
Authors: Jiang Kelly , Saberi Amir , Weber-Levine Carly , Bhimreddy Meghana , Menta Arjun , Routkevich Denis , Davidar Daniel , Quiroz Victor , Hersh Andrew , Luksik Andrew , Khalsa Siri , Liu Ann , Judy Brendan F. , Manbachi Amir , Doloff Joshua , Theodore Nicholas
Published: March 2024

INTRODUCTION:

Stem cells promote spinal cord injury (SCI) recovery by secreting paracrine factors that orchestrate endogenous healing mechanisms. However, effects in clinical trials are modest and there are no approved stem cell therapies to treat SCI. Major barriers include cell washout, immune attack, and oncogenic potential.

METHODS:

ITBs were implanted in three pigs. One pig received a cell-loaded ITB without injury (Cells), another received a cell-loaded ITB with injury (Cells + SCI), and another received a sham ITB with injury (SCI). SCIs were induced by weight drop at T5. ITBs were implanted cranial to the injury and sutured under the dura then loaded with human mesenchymal stem cells or sham cell media. Cerebrospinal fluid (CSF) was collected for 6 days following surgery through a lumbar drain. Cytokines in the CSF were measured by ELISA and the ITB was retrieved for cell viability staining.

RESULTS:

Upon retrieval, stem cells were alive on viability staining of the ITB. CSF levels of the pro-inflammatory cytokines IFNy and IL-1a were increased in the SCI condition compared to the Cells and Cells + SCI conditions. Pro-inflammatory cytokines peaked on post-operative day 5 and remained high. Anti-inflammatory cytokines IL-1ra, VEGF, and TGFβ were elevated in the SCI + Cells condition and depressed in the SCI condition compared to the Cells condition. Anti-inflammatory cytokines peaked on post-operative day 3 and decreased by day 6.

CONCLUSIONS:

In this pilot study, stem cells survived in an implantable ITB and altered cytokine levels in the CSF of pigs with SCI. Cell-loaded ITBs reduced pro-inflammatory cytokines and increased anti-inflammatory cytokines. Implantable ITBs warrant further study as they may represent a potential new delivery option for stem cell therapy.
483 Network Analysis of the Thalamic RNS in Patients With Drug Resistant Epilepsy: Insights to Improve Surgical Targeting
Authors: Subramaniam Varun Ramanan , Avecillas-Chasin Josue Moises , Marcuse Lara , Panov Fedor
Published: March 2024

INTRODUCTION:

Approximately 30% of epilepsy patients are refractory to pharmacotherapy. Patients with drug-resistant epilepsy (DRE) with seizure foci located bilaterally or in the eloquent cortex may be ineligible for resective surgery. For such cases, responsive neurostimulation (RNS) is a viable treatment strategy.

METHODS:

Retrospective analysis of 23 patients treated with thalamic RNS of the centromedian (CM) and anterior nuclei of the thalamus (ANT) from 2015-2022. Clinical features and seizure outcomes were recorded. RNS electrodes were used to model the electrical field using the parameters at last follow up. Patient-specific probabilistic tractography was used to define the network of the seizure onset zone (SOZ) and its thalamic involvement. Each patient’s probabilistic map was used to define the area of highest connectivity of the thalamus with the seizure network. Each of these patient-specific thalamic areas demonstrating highest connectivity with the seizure network were correlated with electrode position, stimulation modeling, and seizure outcomes.

RESULTS:

Seizure network from neocortical areas were highly connected to the CM and from limbic cortical areas to the ANT, MD, and parafascicularis nuclei. Results of the correlation analysis between connectivity, stimulation modelling of the RNS electrode, and seizure outcomes will be presented along with illustrative cases of patient-specific targeting using tractography for RNS placement.

CONCLUSIONS:

Probabilistic tractography is useful to define the networks associated with improved seizure control in thalamic RNS. The identification of these networks prior to surgery could help to identify specific corticothalamic connections and their anatomical trajectories to optimize the implantation of the leads for better and more predictable seizure control.
490 Unilateral Subthalamic Nucleus Deep Brain Stimulation Improves Motor Symptoms Without Neurocognitive Worsening in Parkinsons Disease
Authors: Rogowski Brandon , Salazar Claudia , Rowland Nathan Christopher
Published: March 2024

INTRODUCTION:

Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established surgical intervention for patients with medically refractory Parkinson’s disease (PD). Numerous reports have described adverse nonmotor side effects, such as declines in verbal fluency and working memory, following bilateral implantation. Unilateral STN DBS is a possible alternative; however, it remains unclear whether unilateral implantation meaningfully reduces harmful effects on cognition.

METHODS:

This retrospective cohort study utilized chart review to collect pre- and postoperative Unified Parkinson’s Disease Rating Scale (UPDRS)-III, Levodopa Equivalent Daily Dosage (LEDD), imaging, and neurocognitive test results from 32 patients (unilateral, n = 12; bilateral, n = 20). For all statistical comparisons, p-values less than or equal to 0.05 were considered statistically significant. Student’s unpaired and paired T-tests were used to assess for differences between groups and within groups, respectively.

RESULTS:

There was no difference across 17 preoperative neurocognitive tests. Both unilateral and bilateral STN DBS resulted in significant decreases in postoperative UPDRS-III and LEDD (unilateral: p < 0.0001; bilateral: p < 0.0001) scores. There were no differences in the absolute decreases in UPDRS (p=0.055) and LEDD (p=0.120) scores between the groups. The bilateral STN DBS group had a significant deterioration in verbal fluency (COWAT FAS, p = 0.002; COWAT Animals, p = 0.014) and attention/executive function (Trails A, p=0.049 and Trails B, p = 0.011) compared to the unilateral group.

CONCLUSIONS:

Unilateral STN DBS is an effective and safe treatment option for patients with advanced PD. Particularly for patients with asymmetric motor symptoms, unilateral implantation provides a meaningful improvement in motor symptoms and reductions in dopaminergic medications without the risk of neurocognitive decline seen in bilateral implantation.
506 Deep Learning-Based Image-to-Image Translation to Identify Macrophage Infiltration in High-Grade Glioma Using Label-Free Stimulated Raman Histology
Authors: Alber Daniel Alexander , Lee Sangwon Karl , Smith Andrew , Lock Emily Katherine , Movah-Ezazi; Todd Charles Hollon Misha , Oermann Eric Karl , Orringer Daniel A.
Published: March 2024

INTRODUCTION:

5-Aminolevulinic acid (5-ALA) is the most widely used fluorophore in image-guided glioma surgery, and previous work at our institution demonstrated that 5-ALA highlights tumor-associated macrophages (TAMs) in two-photon microscopy images of brain tumor tissue. Using a unique, paired dataset of stimulated Raman histology (SRH) and two-photon images that share one-to-one spatial resolution, we propose a deep-learning approach to identify macrophages from intraoperative SRH images without requiring fluorescent labels.

METHODS:

We compiled a dataset of 9,554 non-overlapping, 300-by-300 pixel fields of view from paired SRH and two-photon images representing 40 cases of high-grade glioma. A deep generative adversarial network (pix2pix), consisting of a U-Net generator and PatchGAN discriminator, was trained to generate synthetic two-photon images from each SRH patch. The model was trained for 200 epochs, and similarity between the synthetic and real distributions was assessed qualitatively while training and quantitatively using FrÉchet inception distance (FID).

RESULTS:

Our model was successfully trained to generate synthetic two-photon images nearly indistinguishable from ground truth examples. The FID between a held-out test set of real and synthetic images was 8.58, compared to a mean FID of 9.26 ± 0.24 between randomly sampled sets of real images. Our model consistently inferred the location of brightly fluorescing TAMs in held-out, previously unseen test images.

CONCLUSIONS:

We used deep learning to visualize TAMs in label-free SRH images. Analysis of TAM infiltration has the potential to identify patients most likely to benefit from immunotherapy clinical trials. Ongoing work will leverage additional deep-learning approaches to automatically identify and quantify TAM infiltration with SRH, enabling rapid patient-specific analysis of the glioma immune microenvironment.
510 Dopaminergic Neuronal Cell Therapy for Parkinson’s Disease: Results From a Phase 1 Study of Bemdaneprocel
Authors: Tabar Viviane S. , Yu Kenny , Lozano Andres M. , Brennan Cameron Walter , Kalia Suneil K. , Fasano Alfonso , Sarva Harini , Henchcliffe Claire , Yountz Marcus , Enayetellah Ahmed , Lampron Antoine
Published: March 2024

INTRODUCTION:

None of the available therapies for PD directly address the loss of dopaminergic neurons. Bemdaneprocel is an investigational cellular therapy composed of midbrain dopaminergic neuronal cells derived from human embryonic stem cells.

METHODS:

In this open-label study 12 subjects have received 1 of 2 doses of bemdaneprocel to the putamen bilaterally, along with a 1-year immunosuppression regimen. Safety and tolerability have been assessed, along with assessments of engraftment and clinical impact.

RESULTS:

At screening, the average age was 66.4 yrs and the mean time since diagnosis was 9.1 yrs. All subjects presented at screening with a Hoehn and Yahr stage of 2 in the on-medication state. The mean MDS-UPDRS part III score was 46.6 (15-73) when assessed in the off-medication state, and patients presented with 4.3 (1.4-6.2) average daily hours of OFF time as assessed by PD diaries. In both cohorts, the safety profile is favorable with the vast majority of reported treatment-emergent AEs being mild to moderate. All but one AE deemed potentially related to the intervention were attributed to the immunosuppression regimen. There were no AEs reported as possibly related to the cell therapy. Patients enrolled in both cohorts to date have demonstrated clinical improvement as measured by the MDS-UPDRS, PD diaries, PDQ-39, and others. F-DOPA PET imaging supports evidence of engraftment, survival and functionality of the cells at 1 year.

CONCLUSIONS:

Results from at least 1 year of follow-up in this phase 1 study will be presented. An acceptable safety profile, evidence of sustained engraftment, and positive exploratory clinical outcomes in this study support further investigation of bemdaneprocel for the treatment of PD. Unpublished data, will be partly shown in a poster at MDS
698 Animal Model of a Common HFE Mutation Modifies Recovery Following Intracerebral Hemorrhage
Authors: Helmuth Timothy , Kumari Rashmi , Palsa Kondaiah , Neely Elizabeth , Slagle-Webb Becky , Simon Scott , Connor James
Published: March 2024

INTRODUCTION:

Intracerebral hemorrhage (ICH) is a devastating disease with a one-year mortality rate of 45%. In the setting of an ICH, the breakdown of blood releases iron into the brain parenchyma. This excess iron contributes to stroke-induced neurodegeneration as it creates a cytotoxic environment through increased oxidative stress. Genetic variations in iron metabolism such as the H63D HFE mutation have been shown to modify disease progression in neurodegenerative diseases such as Parkinson’s, but have not been studied in ICH.

METHODS:

An autologous blood infusion model was utilized to create an ICH in the right caudate of H67D (human homolog of the H63D HFE mutation) and WT mice. Motor recovery was assessed using latency to fall from rotarod. 3-days post-ICH, the extent of neurodegeneration and mitochondrial damage in glial cells in the perihematomal area were measured using Fluorojade-B (FJB) and Cytochrome-C (CytC) immunofluorescent staining respectively. Levels of key regulatory proteins in the antioxidant and iron storage systems (Nrf2, GPX4, and FTH1) were evaluated using immunoblotting.

RESULTS:

H67D mice demonstrated significantly increased motor recovery at two- and three-days post-ICH compared to WT. H67D mice displayed significantly decreased degenerated neurons and CytC+ glial cells in the perihematomal region compared to WT. Furthermore, levels of Nrf2, GPX4, and FTH1 were significantly increased in the ICH-affected hemisphere of H67D mice.

CONCLUSIONS:

Our data suggest that the H67D HFE mutation modifies ICH recovery through significant improvements in motor recovery and decreases in damaged cells in the perihematomal region. The mechanism appears to be an upregulation of the endogenous antioxidant systems. These data suggest that a study determining the impact of HFE mutations on clinical outcomes in ICH is warranted. Given the prevalence of the H63D HFE mutation in humans, the impact of this mutation on ICH could be highly significant.
701 A Modified Frailty Index to Predict Adverse Outcomes After Decompressive Hemicraniectomy for Acute Ischemic Stroke
Authors: Joshi Krishna C. , Munich Stephan , Kolb Bradley
Published: March 2024

INTRODUCTION:

Surgical decision-making for decompressive hemicraniectomy (DHC) is challenging because of the heterogeneity of health status and the paucity of tools for predicting the operative risk of DHC for malignant edema following acute infarction.

METHODS:

The 2008–2018 National Surgical Quality Improvement Program (NSQIP) data set was accessed for patients undergoing DHC for Acute ischemic stroke (AIS) based on Current Procedural Terminology (CPT) codes. We used a modified frailty index (mFI) based on eleven preoperative clinical NSQIP variables. The outcomes assessed were 30-day occurrences of adverse events.

RESULTS:

A total of 394 patients were identified in the database, there were 55 (14%) patients with mFI 0, 118 patients (30%) with mFI 0.09, 115(29.2 %) with mFI 0.18 and 106 (27%) patients with mFI = 0.27. The rate of return to the operating room for a second procedure significantly increased from 4/55 (7.3%) in patients with mFI 0 to 23/106 (31.1%) in patients with mFI = 0.27. The discharge disposition was significantly different in patients with higher mFI (mFI > 0.27), with only 6/106 (5.7%) discharged to home versus 8/55 (14.5%) with mFI 0. Multivariate logistic regression analysis showed that compared to age, gender, ASA class, and pre albumin levels, mFI was a better predictor of the development of pneumonia (OR 6.278, 95 % CI 1.8, 22.0, p = 0.004) and return to the operating room (OR 4.0, 95 % CI 1.2 ,13.4, p = 0.02).

CONCLUSIONS:

A higher mFI was associated with an increased risk of return to the operating room and worse discharge disposition. The mFI is based on easily identifiable patient characteristics and can be an additional tool to improve perioperative risk stratification in elderly patients considered for DHC after AIS.