bluuebunny/crossref_metadata_2025_split huggingface dataset:
128 NMDA-Receptor Antagonism for the Prevention of Neurological Dysfunction in Traumatic Brain Injury: Results of a Randomized Pre-Clinical Trial
Authors: Maclean Mark , Muradov Jamil , Greene Ryan , Friedman Alon 
Published: March 2023

INTRODUCTION:
Cortical spreading depolarization (CSD) represents a pathomechanistic target for neuroprotective therapy given the association with lesion development and poor outcomes following traumatic brain injury (TBI).

METHODS:
Experiments were conducted using 9-week-old Sprague Dawley rats. Daily neurobehavioral scores were recorded by trained, blinded observers. Using an established weight-drop model, animals received either single moderate (modTBI; n = 23) or four daily mild (rmTBI; n = 30) head impacts. Sham animals received brief anesthetic without TBI (n = 40). Animals underwent cranial window surgery and CSDs were electrically triggered by cortical stimulation; electrophysiological, imaging and blood-flow were monitored using intravital microscopy. Ketamine (100uM topical and 25 mg/kg IP, respectively) and memantine (10 mg/kg IP) were tested in vivo. Subsequently, a RCT was conducted (N=31) using memantine (10 mg/kg) or saline (2.5 cc/kg). Primary outcome: proportion of animals resilient to rmTBI (neurobehavioral scores ≥ 6 out of 12).

RESULTS:
In modTBI, and rmTBI animal models, intraperitoneal ketamine and memantine reduced the proportion of electrically triggered CSDs by 79-88%, and 42-73%, respectively. The average relative amplitude of change in ECoG were reduced by 70-75%, and 51-60%, respectively. Memantine significantly reduced spreading depression and cortical hypoperfusion following CSD. RCT animals in the memantine group were more likely resilient to injury (93% vs. 56%; p = 0.023) and had higher mean neurological scores (9.27 (SD 3.08) vs. 5.56 (SD 3.05)), p < 0.001) compared to saline.

CONCLUSIONS:
The NMDA-receptor antagonist memantine supresses CSDs and reduces pathological cerebral hypoperfusion in vivo following CSDs. In a rmTBI RCT, memantine prevented neurological decline.
141 Polyvinylpyrrolidone-Coated Catheters Show Fewer Astrocytes and Choroid Plexus Epithelium Adhesion and Better Flow/Pressure Performance Than Other Commercial Catheters in a New Catheter Assay System
Authors: Chan Alvin , Ruiz Leandro , Lee Seunghyun , Shah Vaibhavi , Muhonen Michael 
Published: March 2023

INTRODUCTION:
The major cause of failure of cerebral spinal fluid (CSF) shunting devices in pediatric patients is proximal catheter occlusion. There are a number of shunt catheters commercially available, but their occlusion properties are unclear.

METHODS:
There were four catheters tested: 1) antibiotic-impregnated, 2) polyvinylpyrrolidone, 3) barium stripe, and 4) barium impregnated. Catheters were inoculated with cultured astrocytes or choroid cells and incubated in growth media for 7 days prior to testing. Sample catheters were placed into a 3D-printed ventricular replicating system to test occlusion properties. Artificial CSF was pumped through the system to mimic physiologic flow and pressure resistance sensors measured obstruction. Afterward testing, catheters were stained with anti-GFAP or anti-transthyretin to visualize cellular adhesion using a fluorescence microscope.

RESULTS:
Five catheters of each type were used. Polyvinylpyrrolidone catheters had the highest flow (e.g., least obstruction) in the ventricular replication system (0.12 mL/min) compared to the antibiotic coated (0.10 mL/min), barium stripe (0.02 mL/min) or barium impregnated (0.08 mL/min; p < 0.01). Polyvinylpyrrolidone catheters showed the lowest median cell attachment after cell marker staining (<1 cells per 0.07 mm2) compared to antibiotic coated (4.0 cells per 0.07 mm2), barium stripe (3.5 per 0.07 mm2) or barium impregnated (2.0 per 0.07 mm2).

CONCLUSIONS:
Polyvinylpyrrolidone catheters were least likely to be occluded by astrocytes or choroid cells during testing in a novel ventricular replicating system due to lower cellular adhesion. Our findings may have clinical significance when choosing proximal ventricular catheters that are least likely to occlude and prevent proximal shunt failure.
143 Elucidating the Function of the Wnt Signaling Pathway in Hydrocephalus
Authors: Bramall Alexa Natalie , Anton Eva , Lee Amelia , Fecci Peter Edward , Lascola Christopher , Venkatraman Talaignair 
Published: March 2023

INTRODUCTION:
Although acquired hydrocephalus is commonly encountered by neurosurgeons, our understanding of the mechanisms underlying its pathogenesis remain poor. Furthermore, normal CSF physiology is dependent on the proper function of ventricular ependymal cells and choroid plexus epithelium (CPE), although few neurosurgical studies have addressed the functions of these cells.

METHODS:
Alteration of the Wnt pathway is achieved by generating FoxJ1-Cre;Apclox/lox and FoxJ1-Cre;Ctnnb1lox/lox mice, which express Cre upon induction with tamoxifen, as well as via intraventricular delivery of an AAV1-eGFP-Cre in Apclox/lox and Ctnnb1lox/lox mice. T2 weighted MRI with 3D volumetrics is applied to assess ventricular anatomy, in addition to standard molecular biology techniques to examine downstream signaling mechanisms. Kaolin and whole blood injection are used as models of obstructive and communicating hydrocephalus, respectively.

RESULTS:
B-catenin is strongly expressed in adult mouse ependyma and CPE, suggesting that the canonical Wnt pathway continues to be active after these cells have developed. Moreover, up-regulation of this pathway in adult FoxJ1-Cre;Apclox/lox mice results in significant ventricular enlargement (n = 3; p = 0.03). Both FoxJ1-Cre transgenic mice and intraventricular AAV1-eGFP-Cre drive selective expression within ependyma and CPE, suggesting that these may be useful models for investigating important molecular pathways within these cells.

CONCLUSIONS:
Our data suggests that the canonical Wnt signaling pathway plays a role in the maintenance of normal adult CSF dynamics. Moreover, we show selective targeting of ependyma and CPE using an adeno-associated virus, which may represent a novel strategy for modifying genes and/or proteins involved in CSF regulation.
148 Peroneal Nerve Repair With Crossbridge Ladder Technique: Parallel End-to-Side Neurorrhaphies
Authors: Ammanuel Simon , Kim Jason Jungmin , Burkett Daniel , Bond Evalina , Hanna Amgad S. 
Published: March 2023

INTRODUCTION:
Multiple nerve transfer techniques are used to treat patients with nerve injuries when a primary repair is not possible. These techniques are categorized to end-to-end, end-to-side, and side-to-side neurorrhaphy.

METHODS:
Four patients with significant loss of ankle dorsiflexion were seen in the clinic and underwent evaluation, including electrodiagnostic studies. A cross-bridge ladder repair technique was used between the tibial nerve as the donor and the common peroneal nerve as the recipient via one or two nerve grafts coapted in parallel with end-to-side neurorrhaphies. Dorsiflexion strength was measured preoperatively using the Medical Research Council (MRC) grading system and at each postoperative follow-up appointment.

RESULTS:
All four patients had suffered persistent and severe foot drop (MRC of 0) following trauma that had occurred between 6 and 15 months preoperatively. Three of the four patients improved to an MRC of 2 several months postoperatively. The last patient had an immediate improvement to an MRC of 2 by his first month and had a complete recovery of ankle dorsiflexion within four months from surgery.

CONCLUSIONS:
We demonstrate the utility and clinical outcomes of the cross-bridge ladder technique in patients with persistent and prolonged food drop following trauma. Both early and late recovery were seen while all patients regained motor function, with some patients continuing to improve up to the most recent follow-up.
155 Cost-Effectiveness Analysis of Deep Brain Stimulation Versus Treatment as Usual for Treatment-Resistant Obsessive-Compulsive Disorder
Authors: Najera Ricardo Andres , Shofty Ben , Anand Adrish , Gadot Ron , Storch Eric , Goodman Wayne , Sheth Sameer A. 
Published: March 2023

INTRODUCTION:
Deep brain stimulation (DBS) is an effective neurosurgical option for patients with treatment-resistant obsessive-compulsive disorder (TROCD). Despite being more costly than neuroablative procedures of comparable efficacy, DBS has gained popularity for its reversibility. Though its cost-effectiveness has been investigated in movement disorders, few economic analyses of DBS for psychiatric disorders exist.

METHODS:
We developed decision analytic models to compare the cost-effectiveness of DBS to treatment as usual (TAU) for TROCD, varying device type (non-rechargeable or rechargeable) or time-horizon (three or five years). Effectiveness data were based on literature review. Published algorithms were used to convert Y-BOCS scores into utilities. Costs were approached from the healthcare sector perspective and drawn from Medicare reimbursement rates. Monte Carlo (MC) simulations and probabilistic sensitivity analyses were performed to estimate the incremental cost-effectiveness ratio (ICER) in USD ($) per quality-adjusted life-year (QALY).

RESULTS:
We included 238 and 265 TROCD patients across 28 studies who underwent DBS and had sufficient follow-up in our 3- and 5-year models, respectively. Non-rechargeable DBS was less cost-effective than TAU (3-year ICER = $153,221/QALY; 5-year ICER = $194,043/QALY). Rechargeable DBS was moderately more cost-effective at three years (ICER = $70,646/QALY) and definitively more cost-effective at five years (ICER = $37,652/QALY) compared to TAU. At three and five years, net QALYs gained were greater in DBS than TAU by 0.36 and 0.59, respectively. At willingness-to-pay thresholds of $50,000/QALY for definitive cost-effectiveness and $100,000/QALY for moderate cost-effectiveness, rechargeable DBS was moderately more cost-effective than TAU at 3 years in 100% and more cost-effective at 5 years in 96% of iterations.

CONCLUSIONS:
Compared to TAU, in the U.S., rechargeable DBS for TROCD is more cost-effective under a range of possible cost and effectiveness values. However, non-rechargeable DBS is not more cost-effective than TAU for TROCD due to high costs of battery replacement.
167 STA-MCA Bypass for Symptomatic Moyamoya Disease—Lessons Learnt From 89 Revascularisations
Authors: Raheja Amol , Sreenivasan Sanjeev Ariyandath , Suri Ashish , Singh Manmohan , Mishra Shashwat , Tandon Vivek , Phuyal Subash , Devarajan Leve J. , Kalaivani Mani , Chandra Sarat P. , Kale Shashank S. 
Published: March 2023

INTRODUCTION:
Efficacy of surgical revascularisation procedures over conservative management in moyamoya disease (MMD) has been established in the past. However there is dearth of literature on comprehensive evaluation of impact of age and Suzuki staging on clinical and angiographic outcome in symptomatic MMD patients undergoing direct revascularisation (DR) via superficial temporal artery – middle cerebral artery (STA-MCA) bypass.

METHODS:
We analysed consecutive MMD patients who underwent direct-revascularisation (DR) via STA-MCA bypass. Primary outcome measures were mRS scale and stroke risk reduction. Secondary outcome measure was angiographic outcome score (AOS).

RESULTS:
70 patients (89 DR procedures), including 37.9% adults (>18 yr), were operated over a duration of 8 years and followed up for 2 years (mean). Long-term bypass-patency rates were deemed 83.3% and 88.8% in children and adults respectively. In pediatric age group, median mRS scores improved from 3 to 2 (p = 0.001), 97.3% were free of recurrent strokes and AOS scores improved significantly (p = 0.002). Amongst adult MMD patients, median mRS score marginally improved from 3 to 2 (p = 0.25), 100% were free of recurrent strokes and AOS improved significantly (p=0.02). On comparing pediatric and adult patients, improvement in mRS scores (p = 0.14) and AOS scores (p = 0.65) were similar across the two age groups. Overall late stage MMD patients (Suzuki stages IV-VI) showed better improvement in mRS scores when compared with early stage MMD patients (Suzuki stages I-III; p = 0.04). Recurrent stroke rates were similar in both groups (p = 0.26). AOS scores improved significantly in both early and late stage MMD (p < 0.001 in both), though the improvement amongst the two groups was similar (p = 0.88).

CONCLUSIONS:
Using meticulous surgical technique, excellent long-term bypass patency rates can be achieved to facilitate optimal clinical and angiographic outcome in symptomatic MMD patients, irrespective of the age group and stage of disease.
178 Adjunctive Use of Preoperative SPECT Imaging for Evaluation of Chronic Cervical and Lumbar Pain
Authors: Howell Sasha , Saccomano Benjamin Woodrow , Harmon Daniel K. , Okor Mamerhi Otaigbe , Godzik Jakub 
Published: March 2023

INTRODUCTION:
Radionuclide bone scintigraphy with single photon emission computed tomography (SPECT) has been used to evaluate foci of inflammation within the spinal axis. Studies have reported its use as an tool for recognition of pain foci and spondolytic change. As an adjunctive test SPECT may prove to give valuable insight into areas of focal inflammation within the spinal axis and therefore serve as a tool for guiding operative and nonoperative intervention in patients with degenerative spine disease.

METHODS:
We performed a retrospective case series to identify patients with chronic neck/back pain who underwent SPECT imaging for pre-operative evaluation. Patient demographics, area of uptake, correlation with pain morphology, type of intervention, and degree of symptom resolution were quantified. Patients were excluded if they had prior surgery/intervention at the level corresponding to symptomatology.

RESULTS:
Thirty-two patients underwent SPECT imaging. Patients presented with axial back pain (97%) and radicular pain (42%). Radiotracer uptake was seen in facet and/or disc space at the level of symptomology in 44% of patients, facet alone (22%), disc space alone (22%), and uncovertebral joint (12%). Interventions included facet injections (26 patients), basovertebral plexus ablation (7 patients), and open/minimally-invasive surgery (9 patients). Two patients underwent anterior cervical discectomy and the remainder of our cohort underwent lumbar instrumentation and fusion. All but one surgical patient (97%) reported significant relief of symptoms.

CONCLUSIONS:
SPECT imaging may be useful adjunctive imaging modality to evaluate for focal areas of inflammation not readily observed on MRI or CT. Our experience suggests that SPECT can identify areas of pathology that responsive to various types of intervention.
187 Use of Quantitative Pupillometry in Mild Traumatic Brain Injury to Diagnose and Predict Symptom Severity
Authors: Meister Melissa , Aderman Michael , Hershaw Jamie , Ross Jeremy , Roach Megan , Malvasi Steven , Cameron Kenneth , Dengler Bradley 
Published: March 2023

INTRODUCTION:
Concussion screening using the Military Acute Concussion Evaluation (MACE 2) and imaging modalities can be subjective, time intensive, and monopolize scarce resources in a forward deployed environment. The Pupillary light reflex (PLR) has shown recent promise in identifying mild traumatic brain injuries.

METHODS:
Freshman entering a military service academy had baseline PLR measurements (starting pupillary diameter, ending pupillary diameter, average constriction velocity, average dilation velocity, constriction latency, constriction percentage, T75 and pupillary wave form) completed using a Neuroptic PLR-3000. If a subject experienced a concussion they returned for PLR measurements and Sport Concussion Assessment Tool (SCAT) scores within 48 hours of injury.

RESULTS:
Five hundred and fourteen cadets (383 males and 131 females) completed baseline PLR measurements. Sixteen cadets subsequently sustained an mTBI and performed full post-injury assessments. The one-way MANCOVA performed on PLR metrics controlling for symptom severity revealed a marginally significant difference in combined PLR metrics between baseline and post-injury time points [Wilks’ λ = .578, F(8,22) = 2.01, p = .094, partial η = .422]. A significant difference in outcomes between baseline and post-injury were observed for starting pupillary diameter [F(1,29) = 3.10, p = .089, partial η2 = .097], average constriction velocity [F(1,29) = 5.79, p = .023, partial η2 = .167], and maximum constriction velocity [F(1,29) = 4.54, p =.042, partial η2 = .135]. Correlation coefficients demonstrated that post-injury changes in pupillary metrics were strongly associated with post-injury changes in symptom severity, particularly for starting pupillary diameter, constriction percentage, average constriction velocity, maximum constriction velocity, and T75.

CONCLUSIONS:
In this evaluation of service academy cadets there are measurable differences in pupillary dynamics after sustaining an mTBI which correlates with symptom severity.
190 Prion Protein Knockout Leads to Differential RNA Expression Following Head Injury
Authors: Mustroph Christian , Yousuf Seema , Saberian Sepehr , Gimbel David 
Published: March 2023

INTRODUCTION:
It is not well understood why repetitive head injury causes the behavioral and pathologic sequelae associated with Chronic Traumatic Encephalopathy. Cellular prion protein (PrPC) is associated with several neurodegenerative diseases including Alzheimer’s disease and Creutzfeldt-Jakob disease and we have previously demonstrated that PrPC is required for the pathology and behavior associated with CTE after TBI. We show that Prpc knockout leads to differential mice cortex gene expression in a murine repetitive head injury model.

METHODS:
Experimental groups consisted of PrPC-knockout (Prnp-/-) and PrPC wild type (WT) mice. Bilateral close head injury consisted of daily impactions over 10 days with appropriate unimpacted control. All animals were allowed to recover for 6 weeks. Mice were sacrificed and brain cortexes rapidly dissected and flash frozen for RNA extraction, sequencing, and quantification.

RESULTS:
We identified 52 upregulated and 134 downregulated genes in WT impacted compared to unimpacted WT mice. 301 genes were upregulated and 85 downregulated in Prnp-/- impacted mice compared to Prnp-/- mice without impactions. We identified 85 upregulated and 86 downregulated genes in Prnp-/- impacted mice compared to WT impacted mice. RNA expression of KLK6 is upregulated by a factor of 2.3 and KChip3 is downregulated by a factor of 1.3 in Prnp-/- impacted mice compared to WT impacted mice.

CONCLUSIONS:
Deletion of PrPc in a murine model of CTE leads to differential expression of multiple gene clusters. Deletion of Prpc in impacted mice upregulates KLK6 and downregulates KCHip3 which have been implicated in neurodegenerative processes and neuroinflammation including Alzheimer’s disease. We have previously demonstrated that Prpc is required for cognitive deficits and standard histologic pathology following head injury who's biochemical mechanism may implicate KLK6 and KCHip3.
203 Novel Adeno-Associated Viral (AAV) Vectors for Preferential Targeting of Peripheral Nerve Tumors
Authors: Greven Alexander Craig McConnell , Lei Kecheng , Nagarajan Purva , Carneiro Ana , Schafer David , Boulis Nicholas M. 
Published: March 2023

INTRODUCTION:
Definitive treatment for peripheral nerve tumors by surgical excision is associated with significant morbidity. Gene therapy with adeno-associated viral (AAV) vectors is emerging as a promising therapy for these tumors. Directed evolution is a technique that involves applying selective pressure to large libraries of mutated cap genes to bioengineer AAV vectors that selectively bind to and transduce schwannoma tissue.

METHODS:
Tumor samples were harvested from 8 patients and divided for cell culture. Cultures were infected with novel AAV vector C1, novel AAV vector C5, AAV1, AAV2, and AAV6 at MOIs of 2500, 5000, and 10000 for 3-, 7-, and 14-day periods. GFP fluorescence was used to quantify transduction efficiency of each vector. Statistical analysis was performed with one-way ANOVA and student t test.

RESULTS:
AAV2 had significantly higher transduction efficiency at 65% +/- 11 compared to all other vectors (p < 0.001). The remaining order of highest transduction efficiency was novel AAV vector C2 at 21% +/- 4, novel AAV vector C5 at 12% +/- 3, AAV1 at 7% +/- 2, and AAV6 at 6% +/- 2. Higher transduction efficiencies were seen at higher MOIs (2500 vs. 5000 vs. 10000) with no significant difference in cell count (2500: 74.25 +/- 25.59. 5000: 105.50 +/- 15.93, 10000: 90.75 +/- 5.74, p = 0.094). Longer post-infection incubation periods (3-day vs. 7-day vs. 14-day) led to higher transduction efficiencies.

CONCLUSIONS:
AAV2 remains the gold standard for delivery of gene therapy to peripheral nerve tissue. Higher MOIs and longer incubation periods can better differentiate transduction efficiency when comparing multiple AAV vectors without having detrimental effects on cell culture.
213 A Positive Impact on Patterns of Relapse in Diffuse Intrinsic Pontine Glioma after Convection-Enhanced Delivery of Omburtamab
Authors: Bander Evan D. , Garton Andrew L.A. , Pasquini Luca , Yildirim Onur , Ilica Ahmet , Freret Morgan E. , Donzelli Maria , Haque Sofia , Souweidane Mark M. 
Published: March 2023

INTRODUCTION:
Diffuse intrinsic pontine glioma (DIPG) carries a high mortality rate secondary to its aggressive molecular characteristics, infiltrative nature, and lack of effective treatment options. Overall survival is only 9-11 months and median time to progression after radiotherapy is 5-6 months. Convection-enhanced delivery (CED) has demonstrated safety in phase-1 trials, but efficacy is indeterminate.

METHODS:
Sixty-three children with DIPG treated between 2010-2022 were retrospectively reviewed for first radiographic progression. All were treated using conventional external beam radiation (EBRT) and 31 (49%) were treated with CED of radiolabeled 124-Iodine-Omburtamab following EBRT (NCT01502917). Progression was codified by independent neuroradiologists according to anatomic location (local, contiguous, medulla, midbrain, middle cerebellar peduncle (MCP), and/or distant). Overall survival (OS) was assessed with Kaplan-Meier methodology and cumulative incidence of progression at each anatomic site was assessed in a cause-specific competing risk analysis with death as a competing event and were stratified based on CED treatment.

RESULTS:
Mean age at diagnosis was 7.1 (+/-3.4 years) with a median OS of 1.22 years for the cohort. Patients receiving CED demonstrated higher rates of progression in general, when considering progression at all anatomical sites (HR 1.79, p = 0.047) and no statistically significant difference was found in OS when stratified by CED treatment (p = 0.22). However, CED treatment was associated with significantly lower cumulative incidence of pontine and medullary progression (HR 0.43, p = 0.03; HR 0.15, p = 0.01, respectively) relative to non-CED treated patients. No statistically significant differences in progression were identified at other sites (contiguous, midbrain, MCP, or distant).

CONCLUSIONS:
MR-defined patterns of relapse provide evidence for locoregional control in children with DIPG treated with radioimmunotherapy administered by CED. These results prompt a consideration for modifying the design of future clinical trials by supplementing brain stem CED with whole neuroaxis treatment.