bluuebunny/crossref_metadata_2025 huggingface dataset:
166 Trans-radial Versus Trans-femoral Access Routes for Diagnostic Cerebral Angiograms: A Large Single-Center Comparative Cost-analysis Study
Authors: El Naamani Kareem , Atalla Elias , Momin Arbaz , Abbas Rawad , Jain Paarth , Hunt Adam , Sambangi Abhijeet , Carreras Angeleah , El Fadel Omar , Gooch Michael Reid , Tjoumakaris Stavropoula I. , Zarzour Hekmat , Schmidt Richard Frank , Herial Nabeel , Rosenwasser Robert H. , Jabbour Pascal
Published: March 2024

INTRODUCTION:

Recently, the trans-radial approach has become a common alternative given its safety profile and increased patient satisfaction compared to the transfemoral route. Both routes are associated with their respective associated costs and differences typically emerge based on patients’ anatomy, operator expertise, and occurrence of complications.

METHODS:

This a retrospective single-center study of 926 elective diagnostic angiograms performed between December 2019 and March 2022.

RESULTS:

The study comprised of 314 and 612 angiograms done through the TF and TR routes respectively. Female patients were significantly higher in the TF cohort (79.3% vs 67.8%, p < .001), and most other demographic characteristics and baseline modified Rankin Scale score were comparable between both cohorts. The overall cost of patients utilizing the TR route was comparable to that of the TF route ($12591.8 ± 19128 vs $12789.5 ± 18424, p = .88). However, the median cost of catheters was significantly higher in TR group ($55.2 vs $12.4, p = .03), while the median cost of closure devices ($87 vs $20.2 p < .001), and sheaths ($44.6 ± 11.3 vs $41.1 ± 3.1, p < .001) was significantly higher in the TF group.

CONCLUSIONS:

Overall, our study shows that the TR approach can be less a less expensive option for patients undergoing diagnostic cerebral angiograms, especially if complications occur. Future studies can corroborate our findings and potentially lead to the adoption of TR as a low-cost, efficient, gold-standard technique for cerebral angiography.
169 Quantifying the Effect of Fracture Morphology on Nonunion for Traumatic, Isolated Odontoid Fractures Managed Nonoperatively: A Propensity Score Matched Analysis
Authors: Cloney Michael Brendan , Thirunavu Vineeth , Roumeliotis Anastasios , Azad Hooman , Shlobin Nathan A. , Swong Kevin , El Tecle Najib , Dahdaleh Nader S.
Published: March 2024

INTRODUCTION:

Odontoid fractures disproportionately affect older patients who have high surgical risk, but also high rates of fracture nonunion.

METHODS:

We examined all patients with isolated odontoid fractures treated nonoperatively at our institution between 2010 and 2020. Multivariable regression and propensity score matching were used to quantify the effect of fracture type, angulation, comminution, and displacement on bony healing by 26 weeks from injury.

RESULTS:

303 consecutive traumatic odontoid fracture patients were identified, of whom 163 (53.8%) had isolated fractures that were managed nonoperatively. Selection for nonoperative management was more likely with older age (OR = 1.45 [1.14, 1.84], p = 0.003), and less likely with angulated fractures (OR = 0.31 [0.14, 0.65], p = 0.002), or higher presenting Nurick scores (OR = 0.78 [0.63, 0.97], p = 0.023). Factors associated with nonunion at 26 weeks were angulated morphology (OR = 16.14 [2.93, 89.00], p = 0.001) and Anderson-D’Alonzo Type II morphology (OR = 6.54 [2.16, 19.77], p = 0.001). Cox proportional hazards regression demonstrated slower healing time for angulated (HR 0.144 [0.044, 0.377], p = 0.0003) and type II fractures (HR = 0.380 [0.214, 0.673], p = 0.0009). Propensity score matching to assess the effect of type II fracture, fracture angulation, displacement, and comminution all yielded balanced models (Rubin's B < 25.0, 0.5 < Rubin's R < 2.0). By 26 weeks, controlling for confounders, 77.3% of type I or III fractures healed, compared to 38.3% of type II fractures (p = 0.001), and 56.3% of non-angulated fractures healed compared to 12.5% of angulated fractures (p = 0.015). Fracture displacement and comminution had no significant effect.

CONCLUSIONS:

Type II fracture morphology and fracture angulation significantly increase nonunion among nonoperatively managed isolated traumatic odontoid fractures, but fracture comminution and displacement do not.
170 Disc Space Height in Relation to Neural Foraminal Dimensions and Patient Characteristics: A Morphometric Analysis From L1-S1 Using Computed Tomography
Authors: Razzouk Jacob Anees , Vyhmeister Ethan , Carter Mei , Kagabo Whitney , Harianja Gideon Galatoba , Ramos Omar , Wycliffe Nathaniel D. , Douglas Clifford Carl , Cheng Wayne K. , Danisa Olumide A.
Published: March 2024

INTRODUCTION:

The normative relationship between lumbar intervertebral disc space height (DSH) and neuroforaminal dimensions (NFD) has yet to be defined.

METHODS:

Anterior, middle, and posterior DSH were measured on 350 female and 350 male patients between 18 and 35 years of age without spinal pathology. NFD were defined as sagittal anterior-to-posterior (AP) width, axial AP width, foraminal height, and area. Statistical analyses were performed to assess associations among DSH, NFD, and patient height, weight, body mass index, sex, and ethnicity.

RESULTS:

DSH measurements demonstrated increasing, linear trends moving caudally from L1-L2 to L5-S1, while NFD demonstrated a unimodal distribution pattern with largest NFD at L3-L4 and smallest NFD at L1-2 and L5-S1. Accounting for confounding due to height, weight, and ethnicity, male patients demonstrated larger DSH compared to female patients across all levels L1-S1 (p < .001). Asian patients demonstrated taller DSH compared to Caucasian, Hispanic, and African-American patients across all levels L1-S1 (p = .014). Zero moderate or strong correlations were observed between DSH and NFD measurements or patient characteristics for all levels L1-S1, though weight and foraminal height were weakly (r = .3) associated with increased DSH (p < .001).

CONCLUSIONS:

This study describes 38,500 CT-based L1-S1 disc space height and neuroforaminal measurements in young patients without spinal pathology. Among these patients, disc space height follows an increasing trend moving caudally from L1-S1, while foraminal dimensions demonstrate a unimodal distribution clustered at L3-L4. Neuroforaminal dimensions, including foraminal height, are not moderately or strongly associated with disc space height. Disc space height is influenced by sex and ethnicity but is not moderately or strongly influenced by patient height, weight, and BMI.
171 Not Just a Matter of Retained Embryonic Spinal Cord: Histopathology of the Filum Terminale in Tethered Cord Syndrome
Authors: Abdulrazeq Hael , Tang Oliver Young , Leary Owen P. , Ayala Cameron , Najib Hebah , Gokaslan Ziya L. , Donahue John , Klinge Petra Margarete
Published: March 2024

INTRODUCTION:

We present a large consecutive series of patients with tethered cord syndrome who underwent resection of the filum terminale (FT) and the histopathologic findings as analyzed by the neuropathologists.

METHODS:

FT specimens obtained from a consecutive series of 288 pediatric and adult patients that underwent spinal cord releases performed at a single academic institution from 2013-2021 were analyzed retrospectively (IRB #787945). Hematoxylin and eosin (HE) and immunohistochemistry staining was performed to study the spectrum of cells known to reside in connective tissues.

RESULTS:

The most common structures included peripheral nerves (97.6%), ependymal cells (70.8%), ganglion cells (38.5%), and neuropil (15.3%). Cases with excess ependymal cells were associated with ependymal canals (5.9%), ependymal cysts (3.1%), and one case with extensive ependymal “proliferation” (0.3%). With regards to the inflammatory cellular findings, eleven specimens (3.8%) contained scattered or accumulated lymphocytes, macrophages, mast cells, macrophage-derived giant cells, and a secondary lymph follicle in one patient. 36 patients (12.5%) had increased vascularity with enlarged capillaries. Nine patients (3.1%) had an associated type of vascular malformation. A group of specimens included dystrophic calcification within the FT (7.6%).

CONCLUSIONS:

Both vascular and inflammatory changes along with calcifications have been overlooked as possible associated histologic secondary to mechanical stress on the FT. Additionally, vascular anomalies could alter the filum’s mechanical properties due to venous congestion.
177 So the Bone Flap Hit the Floor, Now What?
Authors: Marion Alexis , Lévesque Simon , Touchette Charles , Villeneuve Samuelle-Arianne , Huppé-Gignac Béatrice , Mathieu David , Martin Philippe , Arsenault Christine , Lorio-Morin Christian
Published: March 2024

INTRODUCTION:

Dropping the free bone flap on the operating room floor during a neurosurgical procedure is a rare and poorly documented accident. In fact, it has been reported in up to 3 out of 1000 operations involving craniotomies. The literature guiding its management is insufficient: to date, there is no protocol for sterilization of an accidentally contaminated flap in order to reposition it safely on the patient's skull.

METHODS:

Cadaveric human bone flaps were collected and intentionally dropped onto the floor of a neurosurgical operating room. Bacterial contamination from these flaps was quantified in colony forming units (CFU) counted on culture plates inoculated with the fragments. Identified species were included in a mixed preparation of microorganisms used to artificially contaminate fragments from 29 other individual flaps in a standardized manner. All 29 contaminated flaps were previously cut into five pieces and the following five sterilization protocols were completed on a fragment per flap each: rinsing with saline, mechanical debridement with sterile gauze, rinsing with antibiotics, rinsing with alcoholic chlorhexidine and flash sterilization by autoclave. Decontamination was measured by inoculation onto culture plates and CFU count.

RESULTS:

The observed contamination from a flap dropped on an operating room floor can be significant (up to 120 CFU cultured per flap). All protocols tested decreased bacterial load of the bone flaps to different degrees: saline by 95.7%, mechanical debridement by 97.6%, antibiotic bath by 99.5%, alcoholic chlorhexidine by 99.9% and flash sterilization by 100.0%.

CONCLUSIONS:

In the event of the accidental fall of a bone flap, decontamination by rinsing in an alcohol-chlorhexidine solution, which seems to represent the best combination of effectiveness versus the risks and the complexity of the method, could be considered.
183 Earlier Surgery is Associated With Improved Post-operative Language Development in Children With Tuberous Sclerosis Complex (TSC)
Authors: Sadeghzadeh Sina , Peters Jurriaan , Porter Brenda , Ihnen S. Katie
Published: March 2024

INTRODUCTION:

Early life epilepsy in TSC has been strongly associated with lifelong intellectual disability. While improved seizure control correlates with improvements in quality of life and cognition, the importance of surgery timing in young children has not been well-studied.

METHODS:

Changes in patients’ preoperative (0-12 months) to postoperative (36 months) scores in neuropsychologic tests—including the Mullen Scales of Early Learning (MSEL), Vineland Adaptive Behavior Scales, Second Edition (VABS-II), and the Preschool Language Scales, 5th addition (PLS-5)—were calculated. Pearson correlation and multivariate linear regression models were used to correlate changes in test scores with age at surgery and separately with duration of epilepsy prior to surgery. Analysis was limited to those patients who demonstrated improved seizure control post-operatively (n = 18).

RESULTS:

Age at surgery had a statistically significant negative correlation with changes in the combined verbal sub-tests of the MSEL (R = -0.41, p = 0.04) and predicted the change in that measure outcome in a multivariate linear regression model (β: -0.09, p = 0.03). Similar trends were seen for the change in the total language score of the PLS-5 (R = -0.38, p = 0.06; β: -0.21, p = 0.07). Results were similar when the duration of epilepsy prior to surgery was assessed as the independent variable. However there were no clear trends with the VABS-II questionnaires, even in language domains.

CONCLUSIONS:

Our data shows that successful earlier surgery and shorter epilepsy duration prior to surgery are both associated with improved post-operative language development in a small cohort of patients with TSC. Prospective clinical trials are necessary to further elucidate this relationship.
184 PTEN Mutations Portend Cerebral Ventriculomegaly With Autism-Like Deficits in Cortical Circuitry
Authors: DeSpenza Tyrone , Kizlitug Emre , Allington Garrett , Barson Daniel , O'Connor David , Robert Stephanie , Mekbib Kedous Y. , Singh Amrita , Phan Duy , Nanda Pranav , Mandino Francesca , Constable Todd , Lake Evelyn , Carter Bob S. , Gunel Murat , Lifton Richard , Luikart Bryan , Kahle Kristopher Thomas
Published: March 2024

INTRODUCTION:

Fetal ventriculomegaly, the most common antenatally-diagnosed brain abnormality, is the defining feature of congenital hydrocephalus (CH). Fetal ventriculomegaly is also an overlooked associated finding in neuropsychiatric disorders, including autism spectrum disorder (ASD), which is diagnosed at a 10-fold higher rate in CH patients than in the general population.

METHODS:

We subjected 2,978 parent-trio probands with primary ventriculomegaly, including shunted, sporadic CH, to whole exome sequencing (WES). Using mouse molecular genetics, we generated a novel CH mutant mouse model via prenatal, genetic deletion of a WES-identified CH gene. MRI, measurement of CSF secretion, and cortex-wide, mesoscopic Ca2+ imaging were performed in mice.

RESULTS:

We identify phosphatase and tensin homolog (PTEN) to be the most frequently mutated gene in primary human ventriculomegaly. Integrative analysis of the human fetal brain revealed PTEN was most highly expressed in NKX2.1+ neuroprogenitor cells (NPCs) and their post-natal interneuron descendants. Pten mutant mice with Nkx2.1-specific Pten deletion exhibited neonatal-onset obstructive hydrocephalus, resulting from aqueductal stenosis due to mTor-activated hyperproliferation of NPCs, and CSF hypersecretion due to inflammation-driven choroid plexus hyperplasia. Hydrocephalic Pten mutants also exhibit autism-like hypersynchronization of the somatosensory cortices due to impaired activity of interneurons. Strikingly, genetic or pharmacologic mTORC1 inhibition (everolimus) corrects ventriculomegaly and rescues cortical pathology of Pten mutants.

CONCLUSIONS:

Our data demonstrate that PTEN, a commonly mutated ASD gene, is also the most frequently mutated gene in primary ventriculomegaly. To attenuate the pathologically entangled enlargement of the ventricular system and intrinsic neuronal deficits within the surrounding cortical mantle, the use of rapamycin analogs has high translational potential as an adjunct therapy to neurosurgical CSF diversion in ventriculomegalic patients harboring PTEN mutations. Ventriculomegaly may also be a useful radiographic biomarker for early referral for exome sequencing and formal neurodevelopmental assessments.
185 Deuterium MRI for CSF Studies in Normal and Hydrocephalic Rats
Authors: Hunt Rachel Joy , Nagaraja Tavarekere , Knight Robert , Lee Ian Yu , Ewing James , Penning Donald Henry
Published: March 2024

INTRODUCTION:

The recent characterization of the glymphatic system has revived interest in the interaction of cerebrospinal fluid (CSF) with brain tissue via perivascular spaces. Traditional CSF tracers, such as gadolinium and iohexal, are large molecules that do not cross the blood brain barrier (BBB). The primary component of CSF, however, is water, which is BBB permeable.

METHODS:

Eight adult male rats underwent cisterna magna catheterization for intrathecal infusion. Brain MR images were obtained in a 7 tesla small-animal MRI system. Temporal T1-weighted images (T1WI) were obtained before, during, and after intrathecal infusion of D2O. Five rats then underwent ventricular kaolin injection for induction of hydrocephalus, after which repeat imaging with intrathecal D2O infusion was performed.

RESULTS:

Intrathecal deuterium infusion produced consistent changes on MRI imaging. Because conventional MRI does not sense deuterium, the T1WI showed a loss in proton signal with D2O infusion. Rapid D2O uptake of <2.5 minutes was noted in CSF spaces, brain tissue, and saggital and straight venous sinuses.

CONCLUSIONS:

Use of deuterium as an intrathecal contrast agent provides a physiologically realistic model of CSF behavior. Efforts are ongoing to quantify the relationship between MRI signal loss and deuterium tissue concentration for comparative analysis between healthy and hydrocephalic rats. The loss of MRI signal in the straight sinus after intrathecal infusion implicates the deep venous system in the clearance of CSF, suggesting that CSF is reabsorbed into the venous system via the brain tissue itself. Because traditional CSF tracers do not cross the BBB, the role of the brain tissue in the reabsorption of CSF has been overlooked.
186 Outbreak of Bacterial Subdural Empyema in Pediatric Patients After Relaxation of COVID-19 Non-pharmaceutical Interventions (NPIs)
Authors: Garcia David Matthew , Yekzaman Bailey R.
Published: March 2024

INTRODUCTION:

Non-pharmaceutical interventions (NPIs), in response to the COVID-19 viral pandemic altered viral transmission. In addition, endemic viral strains (influenza, RSV, etc) also experienced unprecedentedly low infection rates. Endemic viral infections typically followed seasonal outbreak spikes, but these spikes were noticeably absent in the COVID-19 control period. After many COVID-19 restrictions were ceased, there was an unusually high spike in endemic viral infections. Many COVID-19 measures were relaxed in the early/middle part of 2021, and we noted a sharp increase in post-viral, complicated sinusitis/subdural empyema cases.

METHODS:

Data collection was via retrospective chart review of subdural empyema cases at our institution. “Post-viral” was defined as positive viral test or VURI symptoms within 30 days.

RESULTS:

Our group previously published our case series on the management of subdural empyema. That served as an historical cohort of 16 patients and 23 procedures over an 8 year period (July 2013-June 2021). During the previous academic year, July 2021 to June 2022, there were a total of 14 patients and 19 surgeries, which nearly doubles the previous 8 years combined. The current academic year (to date) has had 9 empyema patients and 12 surgical cases. 100% of patients in the previous 2 years has had historical symptoms of viral URI symptoms or positive viral URI testing within 30 days. None were documented positive for COVID-19. In less than 2 years since many NPIs were lifted, post-viral, bacterial empyema cases have increased dramatically by a fold of 2.56.

CONCLUSIONS:

NPIs may have created an endemic viral “immunity gap” and an immunologically susceptible population, and thereby could have contributed to a sharp increase in bacterial subdural empyema.
188 Timing of Nerve Reconstruction Surgery to Optimize Long-Term Recovery at the Elbow and Forearm in Neonatal Brachial Plexus Palsy
Authors: Muhlestein Whitney , Chang Kate , Justice Denise , Nelson Virginia , Saadeh Yamaan S. , Smith Brandon W
Published: March 2024

INTRODUCTION:

Restoration of elbow flexion is highly prioritized in nerve reconstruction for neonatal brachial plexus palsy (NBPP). Elbow extension and forearm supination are also frequently impacted in NBPP. Timing of surgical reconstruction for optimal outcomes at the elbow and forearm remains unknown.

METHODS:

We interrogated a prospectively collected database of all children with NBPP who underwent nerve reconstruction at a single center between 2005-2020. AROM was collected for elbow flexion and extension and forearm supination at every clinic visit and normalized between 0 and 1. The cohort was divided into those with surgery =6 months old, 6-9 months old, and >9 months old. We compared elbow and forearm AROM in local age windows between the groups using a regression model expressing the expected AROM as a linear function. Significant differences between the groups were identified using a Wald test.

RESULTS:

Of 99 included children 28 had surgery =6 months old, 46 had surgery between 6-9 months, and 25 had surgery >9 months. At ∼13 years follow up, there was no difference in recovery of AROM for elbow flexion between the groups. For elbow extension, mean normalized AROM was significantly worse when comparing the >9 month and =6 month group (0.41 vs 0.84, p < 0.001). For forearm supination, the =6 month group had significantly better AROM than the 6-9 month (0.57 vs 0.77, p = 0.02) and >9 month (0.46 vs 0.77, p < 0.001) groups. Children who presented earlier had surgery at a younger age.

CONCLUSIONS:

Earlier surgery may result in better long-term recovery of elbow extension and surgery =6 months of age may yield the best outcomes for forearm supination. Early referral may help optimize timing of nerve surgery.
196 Quantifying Cholinergic Cortical Response to Deep Brain Stimulation in Murine Models
Authors: Oliver Tucker , Shanazz Khadijah , Pennington Kendyl , Blake David , Vale Fernando L.
Published: March 2024

INTRODUCTION:

Deep brain stimulation has become a potential treatment for mental disorders. We have previously documented that chronic, one-hour daily, intermittent stimulation of the basal forebrain causes increases in cortical levels of acetylcholine and demonstrates improvement in working memory behavior in monkeys and mice. Continuous stimulation, in contrast, appears to deplete releasable acetylcholine in roughly one minute (Blake et al., Brain Stimulation, 2023; 16(1): 364). This study serves as the first quantification of cortical acetylcholine response to stimulation.

METHODS:

Viral vectors encoding cell surface receptors fluorescent to acetylcholine are injected into superficial cortex in mice through a small craniotomy. After three weeks, the craniotomy is enlarged for glass window affixation above the injection site. Electrodes are implanted posteriorly and angled to contact the basal forebrain. Cortical expression of acetylcholine in response to stimulation is visualized via two-photon microscopy through the window and quantified over time.

RESULTS:

Preliminary data suggest that the physiologic half-life of acetylcholine in the cerebral cortex is 10-12 seconds. Also, the system expressed acetylcholine at normal levels after 20 minutes following 100 seconds of 60Hz stimulation (6000 total pulses). Based on these observations, each second of 60 Hz stimulation of the basal forebrain requires 12 seconds of recovery time.

CONCLUSIONS:

These data are foundational for future explorations in developing treatments for pathology involving cholinergic exchange and recycling, with implications in optimizing deep brain stimulation and tailoring pharmaceuticals that augment acetylcholine reuptake. These data also suggest that high-frequency stimulation decreases neurotransmitter output through depletion. Additional experimentation in the future will incorporate acetylcholinesterase inhibitors and additional stimulation patterns to assess clinical response.
197 Pre-clinical Ex-vivo Study of a 3D Neuronavigation With a Neurosurgical Microrobot
Authors: Andre Arthur , Garvayo Marta , Oulmas Ali , Francois Quentin , Chalivoy Lucas , Zarader Pierre , Ibrahim Souha , Gallardo Oscar , Daher Georges , Nascimento Leandro , Duplat Bertrand
Published: March 2024

INTRODUCTION:

Access to deep brain structures for diagnostic and therapeutic purposes remains a challenge for neurosurgeons. To solve this obstacle, we are developing a micro-robot with the technology to navigate the brain with 3D curved trajectories that will open a new range of possibilities in the neurosurgical world (tumor identification, treatment of epileptic foci, DBS, targeted therapies, fenestration of membranes). The microrobot is tracked and navigated with a transcranial ultrasound system.

METHODS:

10 cadaveric studies were performed using 4 adult swine and 6 human subjects using micro-robot models with diameters of 4.5 mm and 2.9 mm. The microrobotic base for injection and ultrasound tracking of the microrobot (CAP) was placed on the skull at the insertion hole. The micro-robot was remotely controlled, and the surgeries were performed in a hybrid operating room with 3D fluoroscopy, allowing us to validate the surgery feasibility and evaluate the accuracy of the transcranial tracking.

RESULTS:

20 burr holes were performed with holes ranging from 4-9 mm in diameter. The microrobot was inserted successfully infall cases. The navigation was effective with straight or curved trajectories in 18 cases and the targeted points were reached in 16 cases. We observed a mean 3D tracking accuracy of 1.49mm with a S.D. of 0.58 mm, demonstrating a millimetric tracking accuracy, similar to the best stereotaxy performance.

CONCLUSIONS:

These results are a world first, proving the feasibility of intracerebral parenchymal microrobotic neuro-navigation with a millimetric ultrasound transcranial tracking. Future tests will allow testing new prototypes of 1.8mm diameter enabling clinical translation.
198 Human Focal Seizures Induce Wavelike States in Bursts of Neuronal Activity
Authors: Diamond Joshua M. , Inati Sara , Zaghloul Kareem A.
Published: March 2024

INTRODUCTION:

Recent advances in high-density microelectrode arrays (MEAs) have allowed clinicians to record from individual neurons (single-unit activity) or from ensembles of neurons (multi-unit activity, MUA) in the human brain. These recordings have yielded fundamental advances both in epilepsy and in normal brain function. However, the properties of bursts of neuronal activity during seizures have not been characterized.

METHODS:

Five patients at our institution were implanted with microelectrode arrays and met inclusion criteria. Bursts were captured using custom code (MATLAB). We used statistical techniques to compute the rate similarity or sequence similarity between any two sequences.

RESULTS:

We found strong internal consistency within groups of pathological discharges -- that is, IED and seizure related bursts -- for both rate and sequence similarity. We found that baseline, IED, and seizure-related bursts all reside in particular subspaces, after dimensionality reduction using UMAP. During seizures, the LFP exhibits strong wavelike properties. Interestingly, the MUA direction echoes that of the LFP in this patient. However, MUA discharges are only partially wavelike. In IEDs, while the LFP is quite wavelike, the MUA does not exhibit wavelike properties. We found that LFP wave directions, for both seizures and IEDs, tend to arise from the seizure source, as determined using the ECoG. The relationship between the ECoG source and the MUA wave direction is less consistent. Seizure sequences start near the baseline subspace. Over time, seizure bursts are recruited to a distinct subspace, at which time they develop wavelike properties.

CONCLUSIONS:

Seizure events induce wavelike states in neuronal bursts. These findings may help explain why seizures alter cognition.
199 Gamma Knife Radiosurgery to Treat Neurofibromatosis Type 2-Associated Meningiomas: A 35 Year Experience and Paradigm for Future Treatment
Authors: Niranjan Ajay , Wei Zhishuo , Taori Suchet , Alamer Othman Bin , Abou-Al-Shaar Hussam , Hadjipanayis Constantinos G. , Lunsford L. Dade
Published: March 2024

INTRODUCTION:

Management of neurofibromatosis type 2 (NF2)-associated meningiomas remains a case-by-case basis, and treatment options vary.

METHODS:

Forty-nine patients (22 male, 44.90%) with 213 NF2-associated meningiomas treated with SRS between 1987 and 2022 were retrospectively reviewed. The median age at SRS was 56 (range: 20-79) years. Twenty-nine (59.18%) patients had pre-SRS surgical resection, and 7 (14.29%) had prior radiotherapy. The median number of meningiomas per patient was 2 (range: 1-17), the median margin dose was 13 (range: 9-16) Gy, and the median cumulative tumor volume per patient was 8.30 (range: 0.10-74.26) cm3.

RESULTS:

Nine patients (18.37%) had local tumor progression. The 1- and 5-year local tumor control rates were 100% and 90.54%, respectively. Tumor volume < 8.30 cm3 was associated with better local tumor control (p = 0.02, HR: 1.06, 95% CI: 1.01-1.12) on multivariate analysis. Twenty-five patients (51.02%) had detection of new growing tumors (DNGT). The 1- and 5-year DNGT rates were 78.05% and 47.38%, respectively. On multivariate analysis, >2 meningiomas at SRS presentation per patient (p = 0.01, HR: 1.09, 95% CI: 1.02-1.17) was significantly associated with DNGT. Neurological symptoms improved in 20 patients (40.82%), remained stable in 28 patients (57.14%), and worsened in 1 (2.04%) patient at a median follow-up time of 81 (range: 6–267) months after SRS. Seventeen (34.69%) patients were deceased at last follow-up, and 4 patients expired due to intracranial disease progression. Two (4.08%) patients developed transient adverse radiation effects; no patients developed secondary malignancies.

CONCLUSIONS:

Single-session SRS can effectively be used to control tumor progression and improve neurological symptoms in NF2-associated meningioma patients while limiting adverse radiation effects.
201 Clear Cell Meningioma Tumorigenesis Is Characterized by Expression of Human Endogenous Retroviruses
Authors: DeBacker Dang Danielle , Doucet-O'Hare Tara , Rosenblum Bruce S. , Mohlin Sofie , Shah Ashish H. , Winson Ho Sze Chun , Vortmeyer Alex , McGavern Dorian , Heiss John D. , Zhuang Zhengping
Published: March 2024

INTRODUCTION:

Human endogenous retroviruses (HERVs) are transcriptionally silenced genetic remnants of ancient exogenous retroviruses in differentiated cells yet critical to early tissue development. We recently found that aberrant expression of HERV-K envelope protein, caused by SMARCB1 mutation, is critical for tumorigenesis in atypical teratoid rhabdoid tumor (AT/RT). Clear cell meningioma (CCM) demonstrates analogous altered chromatin remodeling via SMARCE1 loss of function and syncytial histopathologic features thereby indicating a putative role for HERV expression in CCM tumorigenesis.

METHODS:

Eight CCM samples were evaluated for SMARCE1 status. We then quantified expression of HERV-K envelope and OCT-4 protein, a marker of pluripotency, by immunohistochemistry and compared them using linear regression. Active HERV transcript production was evaluated by RNA in-situ hybridization. Finally, we induced SMARCE1 loss in neural stem cells (NSC’s) and assessed expression of multiple HERV transcripts. We further modeled SMARCE1 knock-down in vivo in a chicken embryo model to evaluate timing of aberrant HERV expression and CCM development.

RESULTS:

All CCM tumor samples demonstrated loss of SMARCE1 and expression of HERV-K-Env and OCT-4 proteins and HERV transcripts. Expression was more robust in syncytial tumor-initiating cells and surrounding extracellular vesicles. HERV-K-Env expression positively correlated with OCT-4 expression (Pearson’s R = 0.7461, p = 0.033). Finally, SMARCE1 knock-down in NSC's and chicken embryos resulted in expression of multiple HERVs, supporting SMARCE1 loss of function as the mechanism of increased HERV expression in our CCM cohort.

CONCLUSIONS:

As mediated by loss of SMARCE1 function, HERV transcription allows for pathogenic exportation of HERV proteins to surrounding cells to maintain pluripotency in both in vitro and in vivo models. Aberrant HERV expression may therefore represent a targetable anticancer pathway for CCM and similar CNS tumors.
202 The Role of Surgical Management for Prolactinoma in the Era of Dopaminergic Agonists: An International Multicenter Report
Authors: Findlay Matt , Sabahi Mohammadmahdi , Azab Mohammed , Drexler Richard , Rotermund Roman , Ricklefs Franz Lennard , Flitsch Jörg , Smith Timothy R. , Kilgallon John , Honegger Jürgen , Nasi-Kordhishti Isabella , Gardner Paul A. , Charl Zachary
Published: March 2024

INTRODUCTION:

Although first-line prolactinoma (PL) management typically involves dopamine agonists (DAs), the role of surgery as a primary therapeutic is being reconsidered given the undesirable side effects of long-term DAs.

METHODS:

Patients surgically treated for PL from January 2017 through December 2020 were identified. Preoperative characteristics and postoperative outcomes were assessed. Multivariate models adjusting for tumor characteristics and surgery complexity identified factors predictive of complications and long-term adverse outcomes.

RESULTS:

Among 272 patients identified (65.1% female), the mean age was 38.0 ± 14.3 years. Overall, 54.4% of PLs were macroadenomas. Most PLs were managed microscopically (69.9%) and fewer endoscopically (29.0%). Although 29.8% of patients experienced at least one early postoperative complication, most were minor (39.3%), with less being major complications (4.4%). The most common major complications were epistaxis and worsened vision. Most minor complications involved electrolyte/sodium dysregulation. Based on available data on follow-up, disease remission on long-term follow-up imaging was achieved in 94.8% of cases, and residual/recurrent tumor was seen in 19.3%. Reoperations were required for 2.9% of cases. Upon multivariate analysis, previous surgery was significantly predictive of intraoperative complications (6.14 OR, p < 0.01) and major complications (14.12 OR, p < 0.01). Previous pharmacotherapy (0.27 OR, p = 0.02) and cavernous sinus invasion (0.19 OR, p = 0.03) were significantly prohibitive against long-term endocrinological cure. Knosp classification was highly predictive of residual tumor or PL recurrence on 6-month follow-up imaging (4.60 OR, p < 0.01).

CONCLUSIONS:

Our results evaluate a modern, multicenter, global series of patients treated for PL. This data serves as a benchmark to compare with DAs and demonstrates that surgery offers high rates of remission with low rates of complications and recurrence. It may be reasonable to consider surgery as an alternative to DAs.
203 RNA Polymerase II Meningioma Mutations Activate Forebrain Neurodevelopmental Pathways
Authors: Clark Victoria Elizabeth , Prager Briana , Wilson-Hawken Susana , Young Richard
Published: March 2024

INTRODUCTION:

RNA polymerase II, which transcribes DNA into RNA, is mutated in a subset of skull base meningiomas. Patient-derived Pol II mutant meningiomas are dysregulated in pathways directing neural crest differentiation and neurodevelopment. The molecular mechanism of the Pol II driver mutation has remained elusive, and may provide novel therapeutic insight.

METHODS:

The POLR2A Q403K meningioma driver mutation was modeled in the mouse embryonic stem cell system using CRISPR-Cas9. Metabolic labeling of nascent RNA was performed with 4-thiouridine (SLAMseq). Pol II ChIPseq was performed to calculate the travel ratio (proportion of initiated Pol II to elongating Pol II). POLR2A Q403K and wildtype mES cells differentiated over 12 days in permissive media, RNA was harvested over multiple days, and RNAseq was performed.

RESULTS:

POLR2A Q403K cells had a global increase in transcription per nascent RNA sequencing, as measured by T>C conversions (p = 5.71x10-66). For active and highly-paused genes, which were enriched for neurodevelopmental pathways (FDR = 3.52x10-25), a left shift in the mean travel ratio revealed defects in pause-release as the mechanism for increased levels of nascent transcription. Recapitulating human disease, POLR2A Q403K mES cells had significant activation of Hedgehog (Padj. = 2.4x10-3) and WNT (Padj. = 5.2x10-3) signaling pathways, and by day 12 of differentiation showed significant upregulation of pathways critical for rostral cortical development including forebrain neuronal differentiation (FDR = 4.86x10-4), telencephalon development (FDR = 4.30x10-4), and neuronal differentiation (FDR = 4.39x10-4).

CONCLUSIONS:

Meningioma Pol II mutations drive global increases in transcription via dysregulation of pause-release. Highly-paused genes, including master regulators of neural development, are disproportionately activated by mutant Pol II. This dysregulation leads to aberrant induction of neurodevelopmental signaling, including Hedgehog and WNT, and provides a rationale for pharmacologic targeting of these pathways.
205 Microglia-Mediated Survival Outcomes in Preoperative Radiation for Glioblastoma: Insights From a Preclinical Model
Authors: Otamendi-Lopez Andrea , Fernandez Gil Beatriz Irene , Vazquez-Ramo Carla A , Cherukuri Yesesri , Herchko Steven , Jentoft Mark E. , Murray Melissa , Asmann Yan , Trifiletti Daniel M. , Sarabia-Estrada Rachel , Quinones-Hinojosa Alfredo
Published: March 2024

INTRODUCTION:

Glioblastoma (GBM) is the most common and devastating primary brain tumor in adults. The current standard of care includes maximal safe resection followed by concurrent radiation and temozolomide-based chemotherapy. However, preoperative radiotherapy is used in different cancer types and commonly used for brain metastasis to shrink tumors, but it has never been used in for primary GBM.

METHODS:

Thirty-nine immunocompromised adult athymic nude female rats were orthotopically engrafted with a GBM1A patient-derived glioma cell line and randomized to either receive radiotherapy prior to tumor resection (RTRE) or postoperative radiotherapy (RERT). The rats received 30 Gy hypofractionated stereotactic radiation in 5 fractions of 6 Gy. Kaplan-Meier curve was used to plot the survival. Hematoxylin-eosin staining, microglia/macrophages using IBA-1 and TMEM119 markers were used in resected and recurrent tumor tissues. Moreover, nuclei area was measured on all tumor samples. Student’s T-test and analysis of variance (ANOVA) were used for statistical analysis.

RESULTS:

Kaplan-Meier analysis showed a significant survival benefit in the RTRE group, with median survival of 18.28 weeks compared to 14.85 weeks for RERT (p < 0.001), which correlated with the time of recurrence. Simultaneously, an increase in the nuclei area was found in the resected tumor tissues from the RTRE group (p < 0.001) and RERT recurrent tumor tissues (p < 0.001). Interestingly, we found lower microglia/macrophage recruitment in RTRE in the recurrent tumors (p < 0.01) and throughout the tumor areas compared to the RERT group.

CONCLUSIONS:

Our study represents the first preclinical study demonstrating the feasibility and longer overall survival using RTRE instead of RERT in vivo. Moreover, RTRE shows an important effect in the macrophages/microglia recruitment and in the immune profile. This suggests strong superiority for new clinical radiation strategies.
212 Differential Immune Cell Recruitment Between Ruptured and Unruptured Intracranial Aneurysms
Authors: Lucke-Wold Brandon
Published: March 2024

INTRODUCTION:

Accumulating evidence implicates infiltrating inflammatory cells in intracranial aneurysms. However, few studies have examined immunological differences between aneurysm rupture statuses.

METHODS:

An established machine-learning deconvolution algorithm was applied on RNA-sequencing data developed from vessel wall tissue of 21 ruptured and 21 unruptured intracranial aneurysms. A validated gene signature matrix of human hematopoietic cell subsets was used to infer the relative fractions of immune cells present within the original aneurysm tissues.

RESULTS:

Deconvolution of the bulk gene expression data showed significantly increased plasma cells, CD8+ T cells, and activated natural killer cells in unruptured aneurysms compared to ruptured aneurysms.

CONCLUSIONS:

Specific lymphoid elements may be involved in an inflammatory reaction prior to intracranial aneurysm rupture.
214 Technical and Clinical Outcomes in Patients With Short-term Repeated Mechanical Thrombectomy: An International Multicenter Study
Authors: Saad Hassan , Zohdy Youssef M. , Howard Brian M. , Cawley C. Michael , Pabaney Aqueel Hussain , Dimisko Laurie , Alawieh Ali M. , Maier Ilko , Spiotta Alejandro M. , Jabbour Pascal , Wolfe Stacey Q. , Rai Ansaar , Kim Joon-Tae , Masitelli Justin Robert , Starke Robert M. , Shaban Amir , Yoshimura Shinichi , De Leacy Reade , Kan Peter T. , Fragata Isabel , Polifka Adam J. , Arthur Adam S. , Park Min S. , Matouk Charles , Levitt Michael Robert , Tjoumarkaris Stavropoula I. , Liman Jan , Fargen Kyle Michael , Grossberg Jonathan Andrew
Published: March 2024

INTRODUCTION:

Endovascular thrombectomy (EVT) remains the standard of care for acute large vessel occlusion (LVO) stroke. However, the safety and efficacy of repeat EVT (rEVT) in recurrent LVO remains unclear.

METHODS:

Data were included from the Stroke Thrombectomy and Aneurysm Registry (STAR) with 21 stroke centers for EVT performed to treat LVO stroke from 2013-2022. Patients undergoing single or rEVT within 30 days were included. Propensity score matching was used to compare patients undergoing single versus rEVT. The primary outcome was the modified Rankin score(mRS) at 90 days, and secondary outcomes were successful recanalization, postprocedural hemorrhage and mortality.

RESULTS:

Out of a total of 7387 patients who underwent EVT for LVO stroke, 90(1.2%) patients underwent rEVT for the same vascular territory within 30 days. The average time to re-occlusion was 5.3±7.3 days, and 41(45.6%) patients required rEVT within 24hrs. Patients undergoing rEVT had comparable rate of good functional outcome and mortality rate, but with but higher rate of symptomatic intracranial hemorrhage compared to a matched cohort of patients undergoing single procedure. There was a significant reduction in NIHSS before rEVT and at discharge (ΔNIHSS=(-)5 ± 1; p = 0.006). The rate of successful recanalization was similar in single and rEVT groups (78% versus 80%, p = 0.78) and between index and rEVT performed on the same patients (79% versus 80%; p = 0.78).

CONCLUSIONS:

Short-term rEVT is associated with comparable functional outcomes but with higher rate of hemorrhagic conversion compared to patients undergoing single EVT.
216 Loss of Endothelial Tissue-Nonspecific Alkaline Phosphatase Exacerbates Microhemorrhages and Neuroinflammation in a Mouse Model of Ischemic Stroke
Authors: Nwafor Divine , Clary Briana , Al-Humaire Muna , Brown Candice
Published: March 2024

INTRODUCTION:

Despite significant progress in treatment strategies, stroke remains a leading cause of mortality and morbidity. Blood-brain barrier dysfunction is coupled to neuroinflammation and poor outcomes post-stroke. Tissue-nonspecific alkaline phosphatase (TNAP) is a glycophosphatidylinositol-linked protein localized to brain microvascular endothelial cells (BMECs). However, TNAP’s role in BMECs remains unclear. Recent in vitro data from our laboratory demonstrates that conditional loss of BMEC TNAP significantly worsened barrier integrity. Importantly, we have shown that TNAP activity is significantly reduced on cerebral microvessels in the penumbra of wild-type stroke mice.

METHODS:

To test this, we generated mice with a conditional deletion of TNAP in endothelial cells (VE-cKO) and compared the results to controls (Alplfl/fl). Six-month-old mice underwent photothrombotic ischemic stroke (PTS) or sham surgery.

RESULTS:

Laser speckle flowmetry confirmed that PTS mice exhibited a sustained loss of cerebral blood flow compared to sham mice (p < 0.0001). No significant differences in cerebral blood flow and infarct size were noted between VE-cKO PTS and Alplfl/fl PTS mice. Seven days post-PTS, mice were euthanized, and brains were evaluated for BBB dysfunction and neuroinflammation. Preliminary evidence demonstrates a significant increase (p < 0.0001) in GFAP-positive astrogliosis in the cortical penumbra of VE-cKO PTS compared to Alplfl/fl PTS mice. Astrogliosis was also coupled to a significant increase in the number of microhemorrhages (p < 0.0001) in VE-cKO PTS compared to Alplfl/fl PTS mice. Interestingly, large molecule BBB permeability evaluation with immunoglobulin G (150 kDa) showed no significant differences between VE-cKO PTS and Alplfl/fl PTS mice.

CONCLUSIONS:

Ongoing studies will quantitatively assess the extent of BBB permeability utilizing fluorescent tracers of varying sizes. Collectively, these results support a novel mechanism through which loss of TNAP activity is linked to brain microvascular dysfunction post-stroke.
217 Early Experience With Robotic Microvascular Anastomoses
Authors: Wiggan Daniel , Rabbin-Birnbaum Corinne , Sangwon Karl Lee , Choudhry Osamah J. , Nossek Erez
Published: March 2024

INTRODUCTION:

Robotics are becoming increasingly widespread within various neurosurgical subspecialties. The adoption of robotic technology within vascular neurosurgery is of great interest, but data pertaining to its feasibility is currently limited.

METHODS:

68 sutures were performed and assessed. 6 anastomoses (3 robotic and 3 hand-sewn) were performed on 1-1.5 mm caliber tubes and recorded with the operative microscope. We separately compared interrupted sutures (from needle insertion until third knot) and running sutures (from needle insertion until stitch pull-out). Average suture timing across all groups was compared using an unpaired student’s T test.

RESULTS:

We compared 29 robotic sutures to 39 hand-sewn sutures. There was no significant difference between the average time/stitch for the robotic running sutures (n = 18) and the hand-sewn running sutures (n = 16) (45.6 s vs. 41.2 s; p-value = 0.3). The average for the first robotic anastomosis (n=7) was significantly longer than the second (n = 11) (56.3 vs. 38.3; p = .03). The first robotic anastomosis had a negative slope (-8.5). Interestingly, both the second robotic end-to-side anastomosis and the hand-sewn control had shallow positive slopes (1.5 and 2.6). The average of the robotic interrupted sutures (n = 11) was significantly longer than the hand-sewn (n = 23) (286 s vs. 70; p<.01). The average time for the first robotic interrupted anastomosis (n = 7) was significantly longer than the second (n = 4) (366.9 s vs. 144.5; p=0.008).

CONCLUSIONS:

Our results indicate that the learning curve for suturing robotic microanastomoses is short and encouraging. Similar performance to hand-sewn running sutures is possible robotically with minimal practice. Although the learning curve for the interrupted group was encouraging, we only reached similar results to hand-sewn in the very last robotic sutures. Overall, the use of robotics warrants further study for potential use in cerebrovascular bypass procedures.