bluuebunny/crossref_metadata_2025_split huggingface dataset:
659 Minimally Invasive Surgery for Spinal CSF-Leaks in Spontaneous Intracranial Hypotension—Technical Aspects and Complications
Authors: Beck Juergen , Hubbe Ulrich , Klingler Jan-Helge , Rölz Roland , Volz Florian , Urbach Horst , Fung Christian 
Published: March 2023

INTRODUCTION:
Spinal cerebrospinal fluid (CSF)-leaks cause spontaneous intracranial hypotension (SIH). In persisting symptoms despite treatment, surgical closure of spinal CSF-leaks is the treatment of choice.

METHODS:
Since April 2019 SIH patients were operated using the minimal invasive technique of tubular retractors. Leaks were sealed using an interlaminar dorsal access and if necessary a transdural route. Neuromonitoring was used for ventral leaks in the first 16 cases. The primary outcome was the benefit of surgery with respect to orthostatic symptoms; secondary outcome was the occurrence of complications.

RESULTS:
Between April 2019 and December 2020 we included 58 patients, mean age 46 years (IQR 36-55), 65% female, with the diagnosis of SIH. We treated 38 ventral leaks, 17 dorsal/lateral leaks, 2 CSF-venous fistulas. In all but two patients (96.6%) the leak could be approached, identified and closed via the tubular retractor. Leaks were visualized via a transdural approach, after cutting the dentate ligament and lateralization of the ventral dura. Microspurs were removed and leaks were closed by sandwich patch using a fibrin sealant patch (ventral leaks) or clipping of the respective nerve root (lateral leaks, CSF-venous fistula). At a median follow up of 21.5 months (IQR 16-28), eight patients were lost to follow up and 45 reported a benefit from surgery with respect to orthostatic symptoms. Mild permanent neurologic deficits occurred in 1.7%, the revision rate due to persisting or recurring leak was 3.4% and the overall revisioin rate was 10.3%.

CONCLUSIONS:
Minimally invasive surgery using tubular retractors of 18-20mm diameter can be safely and effectively performed for closure of spinal dural CSF-leaks in specialized centers.
664 Use of Local Surgical Site Morselized Autograph to Perform Minimally Invasive Transforaminal Lumbar Interbody Fusion to Improve Outcome
Authors: Perez-Cruet Mick J. , Torre Ramiro Antonio Perez de la , Ramanathan Siddharth , Chieng Leon , Black Jordan , Rapp Aaron , Mong Eric 
Published: March 2023

INTRODUCTION:
MI-TLIF has become one of the primary approaches for treating refractory low back pain. Patient outcomes are related to fusion rates. A critical analysis of the impact of surgical site morselized autograph bone (MAB) on patient reported outcomes undergoing MI-TLIF has not been analyzed.

METHODS:
A retrospective analysis of 215 patients who underwent MI-TLIF using MAB. Variables analyzed included age, gender, follow-up period, comorbidities, number/levels of stenosis, estimated blood loss, surgical time, complications in the immediate postoperative period, clinical scales including VAS (Visual Analogue Scale), ODI (Oswestry Disability Index) at 3, 6, 12, 24 -months.

RESULTS:
Average age was 63.8±12.7 years and average BMI was 29.4±6.1 kg/m2 with average follow-up 19.4+/-11.4 months. Co-morbidities included: diabetes (n=34 (15.8%)) and current or former smoker (n = 61 (28.4%)). Pathogy treated included 156 patients with spondylolisthesis (n = 139, grade 1; n = 17, grade 2) and 122 patients with concomitant stenosis with grade 1(n = 20), 2(n = 15), and 3(n = 87). No major operative adverse events were noted, with 2 patients with postoperative infections. Postoperative VAS showed statistically significant improvements at 3 weeks, 1 year, and 2 years compared to baseline levels (p < 0.00001 for all). Improvements in ODI scores were statistically significant compared to baseline at 3 months (p = 0.03) and 2 years (p = 0.016). Of the 54 patients that had comorbid scoliosis, Cobb angle improved from 20±10.6 preoperatively to 16 ± 10.5 postoperatively (p = 0.27). No long-term adverse events occurred. Fusion rate was greater than 95%.

CONCLUSIONS:
MI-TLIF using MAB was highly cost effective, had low complication rates, and significantly improved patient reported outcomes.
672 Diffusion Basis Spectrum Imaging Provides Insights into Cervical Spondylotic Myelopathy Pathology
Authors: Zhang Justin , Javeed Saad , Greenberg Jacob K. , Jayasekera Dinal , Song Chunyu , Dibble Christopher , Blum Jacob , Sun Peng , Song Sheng-Kwei , Ray Wilson Zachary 
Published: March 2023

INTRODUCTION:
Diffusion basis spectrum imaging (DBSI) is a non-invasive quantitative imaging modality that may improve understanding of cervical spondylotic myelopathy (CSM) pathology through detailed evaluations of spinal cord microstructural compartments.

METHODS:
A single-center prospective cohort study enrolled fifty CSM patients and twenty controls from 2018-2020. All patients underwent clinical evaluation and diffusion-weighted MRI, followed by diffusion tensor imaging (DTI) and DBSI analyses. Diffusion-weighted MRI metrics assessed white matter integrity by fractional anisotropy, axial diffusivity, radial diffusivity, and fiber fraction. In addition, DBSI further evaluates extra-axonal changes by isotropic restricted and non-restricted fraction. Including an intra-axonal diffusion compartment, DBSI improves estimations of axonal injury via intra-axonal axial diffusivity. Patients were categorized into mild, moderate, and severe CSM using mJOA classifications. Imaging parameters were compared among patient groups using independent-samples t-tests and ANOVA.

RESULTS:
Twenty controls, 27 mild (mJOA 15-17), 12 moderate (12-14) and 11 severe (0-11) CSM patients were enrolled. All patient-reported outcome measures were worse in CSM patients (all p < 0.001). DTI and DBSI fractional anisotropy, axial diffusivity, and radial diffusivity were significantly different between control and CSM patients (p < 0.05). DBSI fiber fraction, restricted fraction, and non-restricted fraction were significantly different between groups (p < 0.01). DBSI intra-axonal axial diffusivity was lower in mild compared to moderate (mean difference [95% CI]: 1.1 [0.3, 2.1], p < 0.01) and severe (1.9 [1.3, 2.4], p < 0.001) CSM.

CONCLUSIONS:
DBSI offers granular data on white matter tract integrity in CSM that provide novel insights into disease pathology, supporting its potential utility as a biomarker of CSM disease progression.
744 Reducing Implicit Bias in the Neurosurgery Application and Interview Process
Authors: Cobourn Kelsey Diva , Breton Jeffrey Michael , Dowlati Ehsan , Wong Georgia , Pivazyan Gnel , Nair Nathan 
Published: March 2023

INTRODUCTION:
Each year, Neurosurgery residency programs aim to match the best and brightest applicants aspiring to join the field. Traditionally, metrics such as USMLE Step 1 and 2 scores, publications, and medical school grades have played a key role in determining who is interviewed, the interviewers’ impression of the candidates, and subsequently who is most likely to match. However, these evaluative tools are known to reflect biases in the medical and medical education systems, potentially overlooking diverse applicants well-suited for a career in neurosurgery.

METHODS:
During the 2020-2021 and 2021-2022 residency application cycles, our program instituted a new process for reviewing applications, conducting interviews, and generating a final rank list. Each application was reviewed by attending and resident reviewers, who were blinded to potentially biasing information including pictures and board scores. From this review, selected applicants were interviewed using a set of standardized questions, designed to evaluate specific domains essential for success in neurosurgery. Linear regression was performed to determine correlation between traditional metrics and domain-based interview scores and final rank.

RESULTS:
137 applicants were interviewed. There was no significant correlation between rank and Step 1 (p = 0.47, R2 = 0.003) or Step 2 scores (p = 0.16, R2 = 0.014).Interview scores lacked statistically significant association with Step 1 scores (p=0.10, R2=.02), but were found to correlate with Step 2 scores (p = 0.02, R2 = .05).

CONCLUSIONS:
In our two-cycle experience using this new system, we found no correlation between applicants’ Step 1 scores and their interview scores or final rank list position. We propose this as one alternative method to historically biased tools for evaluating neurosurgery applicants.
773 Diffusion-Weighted MRI Tractography of Midline Thalamic Subnuclei Characterizes the Return of Consciousness Following Severe Traumatic Brain Injury
Authors: Saluja Sabir , Saadon Jordan , Cosgrove Megan , Zhang Jason , Huang Chuan , Mikell Charles B. , Mofakham Sima 
Published: March 2023

INTRODUCTION:
The prefrontal projections of the mediodorsal (MD) and central lateral (CL) thalamus have been implicated in the recovery of consciousness following severe traumatic brain injury (sTBI), but their specific roles are unknown. The CL has been proposed to modulate levels of arousal, while the MD modulates attention.

METHODS:
We generated tractograms in 25 patients with sTBI using DSI-Studio. The CL and MD were seeds and the orbitofrontal (OFC), dorsolateral prefrontal (dlPFC), medial prefrontal (mPFC), and anterior cingulate (ACC) cortices were targets. Fractional anisotropy (FA), a measure of tract integrity, and apparent diffusion coefficient (ADC), a proxy for neuronal injury, were computed for each tract and compared between the early (within 30 days post-injury) and late/no command followers. Spearman correlations were calculated between tract FA and ADC and final Glasgow Coma Scale (GCS) scores.

RESULTS:
Tractography revealed significantly increased MD-OFC tract FA in early compared late/no command followers (P = 0.0125). There was a statistically significant decrease in ADC in early compared late/no command followers in CL-dlPFC (P = 0.0281) and MD-dlPFC (P = 0.0454) tracts. GCS scores were significantly correlated with CL-ACC (P = 0.018) and CL-dlPFC (P = 0.0061) FA, and were not found to be significant in all MD tracts.

CONCLUSIONS:
The FA and ADC differences between early and late/no responders implicate tract integrity of the MD-OFC and dlPFC as key mediators in the return of command-following after TBI, respectively. The CL-ACC and CL-dlPFC tract FA were found to be associated with an increased final GCS score, which grades verbal, eye opening and motor responses. Our results corroborate the MD’s involvement in the content of consciousness, distinct from the CL’s in mediating the ascending arousal network.
806 Excess Postoperative Opioid Prescribing in Pediatric Neurosurgery
Authors: Ackerman Laurie L. , Ash Denise , Burroughs Leah 
Published: March 2023

INTRODUCTION:
Introduction: The opioid crisis is worsening in the United States with opioid overdose deaths reaching record highs in 2020. Opioid medications prescribed at hospital discharge provide an unwitting source of excess opioids posing unique risks to pediatric patients, with half of pediatric overdoses in patients <2 years of age. Although legislative efforts have significantly limited opioid prescribing, recent studies suggest these medications may still be overprescribed.

METHODS:
Methods: Pediatric patients undergoing neurosurgical procedures at Riley Hospital for Children were identified prospectively. Surgery type, length of stay, and inpatient use of opioid and nonsteroidal (NSAID) medications were collected. Patients were contacted 7 days after hospital discharge and asked to report the number of post-discharge prescribed opioid and NSAID doses used.

RESULTS:
Results: 119 patients participated. An average of 22.3 doses of opioid medication were prescribed at discharge, with a mean 3.9 doses used at 7 days. Seventeen patients (14.3%) were prescribed concomitant NSAIDs, and 40 patients (33.6%) used zero doses of prescribed opioid medication. Patients aged ≤13 years used less prescribed opioid doses (x̄ = 15.1%) than patients aged 13-17 (x̄=23.8%). Trends toward increased opioid use in patients undergoing spinal procedures were observed. Patients prescribed NSAIDs used 19.4% of opioid doses compared to 17.2% in those not prescribed NSAIDs.

CONCLUSIONS:
Conclusion: Pediatric neurosurgery patients used only 17.5% of prescribed opioids in 7 days after hospital discharge, creating excess unused opioid medication that may increase the risk of accidental ingestion and misuse. Opioid prescription amounts were subsequently limited, and follow-up data collection continues. The present study highlights the need for educational initiatives for providers to minimize excess opioids prescribed and for parents to safely dispose of leftover opioid medication.
831 Evaluation of Trends in Gait Function Following Ventriculoperitoneal Shunt Placement in Patients with Idiopathic Versus Secondary Versus Neurodegenerative NPH: A Long Term Follow-Up of 63 Patients
Authors: Cunningham Coby , Barpujari Awinita , Kujawski Brandon , Thompson Diane , Lonich Ian , Leonardo Jody 
Published: March 2023

INTRODUCTION:
Normal Pressure Hydrocephalus (NPH) most commonly presents in the elderly with symptoms such as gait dysfunction, urinary incontinence, altered mentation. In the current literature three categories of NPH are commonly considered: idiopathic (iNPH), secondary (sNPH), and neurodegenerative (nNPH). Due to variability in the causative pathology, NPH patients in each category may respond differently to ventriculoperitoneal shunt (VPS) placement over the long term.

METHODS:
An IRB approved retrospective review was conducted on 63 patients with diagnosed iNPH, sNPH, or nNPH who underwent shunt placement (2016 - present). Each patient was closely followed by a single surgeon and specialized team at our adult hydrocephalus clinic from time of symptomatic presentation through diagnosis, shunt placement, and post-operative assessments. Assessment at all pre- and post-operative visits included gait assessment via timed 25’ walk test (TW) and timed up-and-go (TUG) test.

RESULTS:
Long-term outcomes for the TW test, measured from baseline to most recent follow-up show that iNPH patients averaged an improvement of 4.83s (seconds), while sNPH and nNPH patients averaged improvements of 4.25s and 2.98s, respectively. Following the TUG test, the average improvement for iNPH patients was 4.37, with the improvement averages for sNPH and nNPH being 15.33s and 3.09s, respectively.

CONCLUSIONS:
There is a noticeable difference in the objective gait measurements at post-shunting follow-up among patients diagnosed with the three major categories of NPH. We believe the root of this variability lies within the specific causative factors for the respective patients’ NPH and may be particularly affected by the progressive degenerative nature of the nNPH category. Careful categorization of patients into each group may aid surgeons as they council their patients and set expectations for realistic post-operative courses.
832 Multiple Computations of Reward-Based Learning are Differentially Encoded in the Human Limbic Network
Authors: Huang Yuhao (Danny) , Kakusa Bina , Shivacharan Rajat , Feng Austin Y. , Parker Jonathon J. , Halpern Casey H. 
Published: March 2023

INTRODUCTION:
Adaptive decision making requires the capacity to anticipate and detect rewarding or aversive outcomes. Prior animal and neuroimaging studies have implicated the limbic network as an important contributor to this process. However, how different limbic regions differ in supporting distinct phases of reward-related computations are not well understood.

METHODS:
Fourteen human participants undergoing electrographic monitoring were included based on implantation with a depth electrode targeting at least one of the following limbic regions: anterior cingulate, hippocampus, amygdala, orbitofrontal cortex, or anterior insula. Participants completed a reinforcement learning task known as the monetary incentive delay (MID) paradigm, which is a widely used computer-based task utilized in neuroimaging research to assay anticipatory and outcome signals to monetary reward and loss. A reinforcement model was constructed based on task behavioral data. Computations of this model were regressed against electrophysiologic signals.

RESULTS:
We found that an expectant value signal was encoded during both reward anticipation and outcome while prediction error was solely encoded in the outcome phase. Broadband gamma activity (25-180 Hz) positively scaled with expectation value and prediction error, while low-frequency activity (1-12 Hz) negatively scaled with prediction error. Limbic regions including the anterior insula, hippocampus, orbitofrontal and anterior cingulate cortices exhibited differential encoding schemes for reward valence. Finally, there was a difference in the distribution of individual channels across limbic regions encoding expectation value, prediction error, or both.

CONCLUSIONS:
These findings indicate spatially distributed limbic regions with their own unique functions support complex computations of reinforcement learning.
835 Rapid Prototyping, Digital Sculpting, and Computer Aided Design for Point of Care 3D Printed Stereo EEG Models
Authors: Austerman Ryan , Faraji Amir H. 
Published: March 2023

INTRODUCTION:
Part of the workup for surgical management of epilepsy is stereotactic placement of intracranial depth electrodes to better understand the origin and network pattern of spread of seizures. To facilitate surgical decision making, epilepsy team discussion, and patient/family communication, a workflow was developed to create 3D printed models of sEEG patient brains and electrode locations which could be invaluable in explaining EEG results and surgical options.

METHODS:
Pre-op MRI and post-implantation CT scans of a sEEG case were imported and merged using 3D Slicer, a free and open-source software package for advanced medical imaging research.The CT was segmented to include only the high-density metallic electrodes. These 3D models were exported into Autodesk Fusion 360, a computer-aided design (CAD) program, where electrode models were designed based on their location on the CT scan. These models were exported to Maxon Zbrush to be cleaned and re-meshed to make the model easier to sculpt and manipulate.The electrode objects were used as cutting tools to create holes in the brain model. Finally, the relevant portion of the brain (right temporal lobe and surrounding regions) and electrodes were exported for 3D printing. The final models were 3D printed on a FormLabs Form 3 stereolithography (SLA) printer using clear resin for the brain and flexible grey resin for the electrodes.

RESULTS:

CONCLUSIONS:
A workflow was devised to print anatomic models of brains implanted with electrodes for seizure monitoring in 2-3 days utilizing software from multiple disciplines including medical imaging, CAD/engineering, and 3D sculpting used in the film and video game industries. Future models will include further anatomical definition with more advanced 3D sculpting and printing techniques.
866 Preclinical Study of Pamiparib, a CNS Penetrant PARP Inhibitor, in IDH1/2 Mutated Gliomas
Authors: Hong Christopher Sungwoon , Sundaram Ranjini , Bindra Ranjit 
Published: March 2023

INTRODUCTION:
Our group demonstrated IDH1/2-mutated gliomas harbor intrinsic homologous recombination (HR) defects mediated by 2-HG, conferring sensitivity to PARP-inhibitors. We studied pamiparib, a CNS-penetrant PARP-inhibitor with potent PARP-trapping ability, in combination with TMZ and radiation in IDH1/2-mutated gliomas and its pharmacokinetics to demonstrate CNS penetrance.

METHODS:
We performed DNA-repair functional studies with in-vitro short- and long-term viability assays, and in-vivo studies utilizing an intracranial rat glioma model with bioluminescence imaging. Pharmacokinetics was measured with LCMS/MS from harvested tumor, normal brain, and blood.

RESULTS:
In-vitro viability assays in paired isogenic IDH1-wildtype and mutant U87 cells showed the IDH1 mutation conferred several-fold enhanced sensitivity to TMZ, as expected. Differential TMZ sensitivity was less pronounced in HCT116 cells, as expected given higher MGMT expression. ELISA confirmed PARylation inhibition by pamiparib at the nanomolar range in a dose-dependent manner. Enhanced pamiparib sensitivity was seen in IDH-mutant U87 and HCT116 cells compared to wildtype. Pamiparib and TMZ demonstrated synergistic interactions in U87 cells, dependent upon IDH1 mutation status. In HCT116 cells, TMZ resistance was overcome with pamiparib in wildtype and mutant cells but notably at lower doses in mutant cells. Synergy was observed with pamiparib and radiation in U87-mutant, compared to wildtype cells. Pharmacokinetics demonstrated favorable CNS penetration with tumor:plasma ratios (>0.20) with 3 mg/kg and 6 mg/kg doses of pamiparib, orally administered BID to rats harboring RG2-cell intracranial tumors. These levels persisted between 2- and 8-hours after last dosing. Pamiparib selectively penetrated tumors over normal brain with normal brain:plasma ratios <0.20.

CONCLUSIONS:
Pamiparib may selectively target IDH1/2-mutated gliomas and act synergistically with TMZ and radiation to exploit intrinsic HR defects. Pharmacokinetics suggest favorable CNS penetration after BID oral administration.
870 Association of MGMT Methylation With Response to Chemotherapy in WHO Grade 2 Low Grade Glioma
Authors: Chalif Eric , Young Jacob , Aghi Manish Kumar 
Published: March 2023

INTRODUCTION:
The role of adjuvant chemotherapy (AC) in the treatment of low-grade glioma (LGG) has been an area of controversy. While of O6-methylgaunine-DNA-methyltransferase (MGMT) promoter methylation is a predictor of response to AC in high grade glioma, its relevance in LGG is uncertain.

METHODS:
Overall survival was evaluated using Kaplan-Meier estimates and multivariable Cox proportional hazards regression. Subgroup analyses were conducted in cohorts defined by tumor size, tumor location, histology, extent of resection, and receipt of radiation.

RESULTS:
Between 2004 and 2018, 1,139 participants were diagnosed with WHO grade 2 LGG (median [IQR] age, 40 years [31-53]; 578 were male [51%]; 614 were MGMT methylated (54%)). In multivariate analysis, among the 512 patients (45%) receiving AC, there was improved overall survival in methylated compared to unmethylated cohorts (hazard ratio [HR], 0.48; 95% CI, 0.32-0.72; p < 0.001). This association was not demonstrated in patients without AC (HR, 1.01; 95% CI, 0.63-1.60; p=0.985). On subgroup analysis, MGMT methylation status was associated with an independent improved response to chemotherapy in subgroups of patients with no 1p/19q codeletion [astrocytoma], tumor diameter ≥50mml, tumor diameter <50mm, frontal lobe tumors, radiotherapy, no radiotherapy, and subtotal resection MGMT methylation was not associated with improved response to chemotherapy in patients with 1p/19q codeletion [oligodendroglioma] or gross total resection.

CONCLUSIONS:
MGMT methylation status was associated with response to AC in adult astrocytic LGG, irrespective of treatment with radiation. This relationship was not present for oligodendroglioma. If replicated in contemporary trials, these findings will substantially guide treatment decisions for many LGG patients.