Neurology Commons^™

Cochlear Implantation After Head And Neck Radiation: A Case Series, Systematic Review, And Meta-Analysis, Jumah G Ahmad, Benjamin D Lovin, Anna Lee, Marc-Elie Nader, Paul W Gidley

Faculty, Staff and Student Publications

Objective: To determine if cochlear implant (CI) is safe and effective in patients with radiation therapy (XRT)-induced sensorineural hearing loss and to discuss considerations in this population through a retrospective cohort review, systematic review, and meta-analysis.

Databases reviewed: PubMed, Cochrane Library, and Embase.

Methods: We retrospectively reviewed all CI cases after head and neck (HN) XRT at our institution, noting intraoperative findings, postoperative complications, and hearing outcomes. Change in speech discrimination scores (SDSs) was the primary outcome measure. Systematic review was performed to identify all cases of CI after HNXRT. A meta-analysis was performed to assess SDS change.

Results: The …

Risk Factors For In-Hospital Seizure And New-Onset Epilepsy In Coiling And Clipping Treatment Of Aneurysmal Subarachnoid Hemorrhage, Viet-Thang Le, Anh Minh Nguyen, Phuc Long Nguyen

Faculty, Staff and Student Publications

OBJECTIVE: To identify risk factors associated with in-hospital seizures and new-onset epilepsy in patients with aneurysmal subarachnoid hemorrhage (SAH) who underwent coiling embolization or clipping surgery.

METHODS: This retrospective descriptive study included 195 patients diagnosed with aneurysmal SAH and treated with coiling embolization or clipping surgery between January 2018 and June 2022.

RESULTS: Among the 195 patients meeting inclusion criteria, 9 experienced an onset seizure at the time of SAH. In-hospital seizures were observed in 33 patients, of which 24 were electrographic seizures detected in 24 patients with suspected subclinical seizures. After 12 months of follow-up, 11 patients met criteria …

Blockade Of Rho-Associated Kinase Prevents Inhibition Of Axon Regeneration Of Peripheral Nerves Induced By Anti-Ganglioside Antibodies, Andrés Berardo, Cristian R Bacaglio, Bárbara B Báez, Rubén Sambuelli, Kazim A Sheikh, Pablo H H Lopez

Faculty, Staff and Student Publications

Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrè syndrome, mostly related to halted axon regeneration. Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration. These effects involve the activation of the small GTPase RhoA/ROCK signaling pathways, which negatively modulate growth cone cytoskeleton, similarly to well stablished inhibitors of axon regeneration described so far. The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632, a selective pharmacological inhibitor of ROCK, in a mouse model of axon …

Activation Of Cerebral Ras-Related C3 Botulinum Toxin Substrate (Rac) 1 Promotes Post-Ischemic Stroke Functional Recovery In Aged Mice, Fan Bu, Jia-Wei Min, Md Abdur Razzaque, Ahmad El Hamamy, Anthony Patrizz, Li Qi, Akihiko Urayama, Jun Li

Faculty, Staff and Student Publications

Brain functional impairment after stroke is common; however, the molecular mechanisms of post-stroke recovery remain unclear. It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke. Mounting evidence suggests that axonal regeneration and angiogenesis, the major forms of brain plasticity responsible for post-stroke recovery, diminished with advanced age. Previous studies suggest that Ras-related C3 botulinum toxin substrate (Rac) 1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model. Here, we investigated the role of Rac1 signaling in long-term …

Efficacy And Safety Results After >35 Years Of Treatment With The Bruton’S Tyrosine Kinase Inhibitor Evobrutinib In Relapsing Multiple Sclerosis: Long-Term Follow-Up Of A Phase Ii Randomised Clinical Trial With A Cerebrospinal Fluid Sub-Study, Xavier Montalban, Karolina Piasecka-Stryczynska, Jens Kuhle, Pascal Benkert, Douglas L Arnold, Martin S Weber, Andrea Seitzinger, Hans Guehring, Jamie Shaw, Davorka Tomic, Yann Hyvert, Danielle E Harlow, Martin Dyroff, Jerry S Wolinsky

Faculty, Staff and Student Publications

BACKGROUND: Evobrutinib - an oral, central nervous system (CNS)-penetrant, and highly selective Bruton's tyrosine kinase inhibitor - has shown efficacy in a 48-week, double-blind, Phase II trial in patients with relapsing MS.

OBJECTIVE: Report results of the Phase II open-label extension (OLE; up to week 192 from randomisation) and a cerebrospinal fluid (CSF) sub-study.

METHODS: In the 48-week double-blind period (DBP), patients received evobrutinib 25 mg once-daily, 75 mg once-daily, 75 mg twice-daily or placebo (switched to evobrutinib 25 mg once-daily after week 24). Patients could then enter the OLE, receiving evobrutinib 75 mg once-daily (mean (± standard deviation (SD)) …

Association Of Hematological And Biochemical Parameters And Hla-Drb1 Alleles With Anti-Cyclic Citrullinated Peptide Autoantibodies In Sudanese Rheumatic Patients, Khalid E Khalid

Faculty, Staff and Student Publications

Introduction

Anti-citrullinated protein/peptide antibodies (ACPA) are crucial for the diagnosis and prognosis of rheumatoid arthritis (RA) and are associated with class II HLA-DRB1 alleles.

The study’s goal was to determine how DRB1 alleles and hematological and biochemical parameters affect ACPA production in RA patients from Sudan.

Methods

The study analyzed the hematological and biochemical parameters and the frequency of HLA-DRB1 alleles in 120 RA patients and 100 controls. Automated analyzers, ELISA, the latex agglutination test, and the Westergren method were utilized for hematological and biochemical testing. HLA class II alleles were genotyped using polymerase chain reaction-sequence-specific primers (PCR-SSP). The student’s …

The Design Of A Quality Improvement Dashboard For Monitoring Spinal Cord And Column Injuries, Zahra Azadmanjir, Mohsen Sadeghi-Naini, Mohammad Dashtkoohi, Maziar Moradi-Lakeh, Jalil Arabkheradmand, James Harrop, Vafa Rahimi-Movaghar

Department of Neurosurgery Faculty Papers

Background: Interactive dashboards are a powerful tool for dynamic visualization and monitoring of patient performance and serve as a useful to for optimal decision-making. The National Spinal Column and Cord Injury Registry of Iran (NSCIR-IR) was designed to efficiently display and broadcast important patient care data. This has been achieved through an electronic dashboard display (graph and visual displays), rather than traditional static paper reports (text). Objectives: The objective of this study was to design and develop an electronic visual dashboard as a display system to monitor the quality of care in the NSCIR-IR collaborating centers. Methods: The indicators chosen …

Novel Approach To Difficult Spinal Reconstruction: Bilateral Simultaneous Rib And Iliac Crest Vascularized Bone Graft Spinoplastic Surgery, Maria Shvedova, Isra Abdulwadood, Daniel M Vernik, Max A Shrout, Jonathan L Jeger, Dylon C Buchanan, Alexander Ropper, Sebastian Winocour, Michael Bohl, Maziyar A Kalani, Edward M Reece

Faculty, Staff and Students Publications

Pseudoarthrosis is a severe complication of spinal fusion surgery with occurrence rates as high as 35%-40%. Current options of revision surgery to correct pseudoarthrosis frequently carry high failure rates and risk of developing junctional kyphosis. Pedicled vascularized bone grafts (VBGs) are an innovative approach to boost spinal fusion rates via improving structural integrity and increasing the delivery of blood to the donor site. This versatile technique can be performed at different spinal levels without additional skin incisions and with minimal added operative time. Here we present the first bilateral rib and iliac crest VBG spinoplastic surgery performed to augment spinal …

Glial Lipid Droplets Resolve Ros During Sleep, Lindsey D Goodman, Matthew J Moulton, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

The Sehgal lab presents data showing that the non-cell autonomous pathway of glial lipid droplet formation occurs during sleep and helps to resolve neuronal reactive oxygen species (ROS). This promotes neuronal function after an active day. Hence, this pathway has an important physiological function beyond its previously described role in ROS-associated diseases, including Alzheimer’s disease.

Signaling Mechanisms Underlying Activity-Dependent Integration Of Adult-Born Neurons In The Mouse Olfactory Bulb, Suyang Bao, Juan M Romero, Benjamin D W Belfort, Benjamin R Arenkiel

Duncan NRI Faculty and Staff Publications

Adult neurogenesis has fascinated the field of neuroscience for decades given the prospects of harnessing mechanisms that facilitate the rewiring and/or replacement of adult brain tissue. The subgranular zone of the hippocampus and the subventricular zone of the lateral ventricle are the two main areas in the brain that exhibit ongoing neurogenesis. Of these, adult-born neurons within the olfactory bulb have proven to be a powerful model for studying circuit plasticity, providing a broad and accessible avenue into neuron development, migration, and continued circuit integration within adult brain tissue. This review focuses on some of the recognized molecular and signaling …

An Evidence-Based Update On Anticholinergic Use For Drug-Induced Movement Disorders, Nora Vanegas-Arroyave, Stanley N Caroff, Leslie Citrome, Jovita Crasta, Roger S Mcintyre, Jonathan M Meyer, Amita Patel, J Michael Smith, Khody Farahmand, Rachel Manahan, Leslie Lundt, Samantha A Cicero

Faculty, Staff and Students Publications

Drug-induced movement disorders (DIMDs) are associated with use of dopamine receptor blocking agents (DRBAs), including antipsychotics. The most common forms are drug-induced parkinsonism (DIP), dystonia, akathisia, and tardive dyskinesia (TD). Although rare, neuroleptic malignant syndrome (NMS) is a potentially life-threatening consequence of DRBA exposure. Recommendations for anticholinergic use in patients with DIMDs were developed on the basis of a roundtable discussion with healthcare professionals with extensive expertise in DIMD management, along with a comprehensive literature review. The roundtable agreed that "extrapyramidal symptoms" is a non-specific term that encompasses a range of abnormal movements. As such, it contributes to a misconception …

Cognitive Function Remains Associated With Functional Impairment In Profound Dementia: Alzheimer Disease And Dementia With Lewy Bodies, Ihika Rampalli, Valory N Pavlik, Melissa M Yu, Jeffrey Bishop, Chi-Ying R Lin

Faculty, Staff and Students Publications

Background and objectives: The Baylor Profound Mental Status Examination (BPMSE) was developed to assess cognitive function in the profound stage of dementia. The Clinical Dementia Rating (CDR) scale has been widely used in measuring functional performance in dementia. We aimed to determine whether cognitive function is related to overall functional impairment in profound dementia.

Methods: We selected 864 patients with probable Alzheimer disease (AD) and 25 patients with possible dementia with Lewy Bodies (DLB) cases with profound dementia by Mini-Mental Status Examination or/and clinical global impression. We used BPMSE to measure cognitive function and the CDR sum-of-boxes (CDR-SB) score to …

Virtual Multi-Institutional Tumor Board: A Strategy For Personalized Diagnoses And Management Of Rare Cns Tumors, James L Rogers, Thomas Wall, Alvina A Acquaye-Mallory, Lisa Boris, Yeonju Kim, Kenneth Aldape, Martha M Quezado, John A Butman, James G Smirniotopoulos, Huma Chaudhry, Christina I Tsien, Prashant Chittiboina, Kareem Zaghloul, Orwa Aboud, Nicholas G Avgeropoulos, Eric C Burton, David M Cachia, Karan S Dixit, Jan Drappatz, Erin M Dunbar, Peter Forsyth, Edina Komlodi-Pasztor, Jacob Mandel, Byram H Ozer, Eudocia Q Lee, Surabhi Ranjan, Rimas V Lukas, Margarita Raygada, Michael E Salacz, Matthew A Smith-Cohn, James Snyder, Ariane Soldatos, Brett J Theeler, Brigitte C Widemann, Kevin A Camphausen, John D Heiss, Terri S Armstrong, Mark R Gilbert, Marta Penas-Prado

Faculty, Staff and Students Publications

PURPOSE: Multidisciplinary tumor boards (MTBs) integrate clinical, molecular, and radiological information and facilitate coordination of neuro-oncology care. During the COVID-19 pandemic, our MTB transitioned to a virtual and multi-institutional format. We hypothesized that this expansion would allow expert review of challenging neuro-oncology cases and contribute to the care of patients with limited access to specialized centers.

METHODS: We retrospectively reviewed records from virtual MTBs held between 04/2020-03/2021. Data collected included measures of potential clinical impact, including referrals to observational or therapeutic studies, referrals for specialized neuropathology analysis, and whether molecular findings led to a change in diagnosis and/or guided management …

Neural And Behavioural State Switching During Hippocampal Dentate Spikes, Jordan S Farrell, Ernie Hwaun, Barna Dudok, Ivan Soltesz

Faculty, Staff and Students Publications

Distinct brain and behavioural states are associated with organized neural population dynamics that are thought to serve specific cognitive functions^1–3. Memory replay events, for example, occur during synchronous population events called sharp-wave ripples in the hippocampus while mice are in an ‘offline’ behavioural state, enabling cognitive mechanisms such as memory consolidation and planning^4–11. But how does the brain re-engage with the external world during this behavioural state and permit access to current sensory information or promote new memory formation? Here we found that the hippocampal dentate spike, an understudied population event that …

Challenges And Considerations Of Preclinical Development For Ipsc-Based Myogenic Cell Therapy, Congshan Sun, Carlo Serra, Brianna Harley Kalicharan, Jeffrey Harding, Mahendra Rao

Faculty, Staff and Students Publications

Cell therapies derived from induced pluripotent stem cells (iPSCs) offer a promising avenue in the field of regenerative medicine due to iPSCs' expandability, immune compatibility, and pluripotent potential. An increasing number of preclinical and clinical trials have been carried out, exploring the application of iPSC-based therapies for challenging diseases, such as muscular dystrophies. The unique syncytial nature of skeletal muscle allows stem/progenitor cells to integrate, forming new myonuclei and restoring the expression of genes affected by myopathies. This characteristic makes genome-editing techniques especially attractive in these therapies. With genetic modification and iPSC lineage specification methodologies, immune-compatible healthy iPSC-derived muscle cells …

Sans-Cnn: An Automated Machine Learning Technique For Spaceflight Associated Neuro-Ocular Syndrome With Astronaut Imaging Data, Sharif Amit Kamran, Khondker Fariha Hossain, Joshua Ong, Nasif Zaman, Ethan Waisberg, Phani Paladugu, Andrew Lee, Alireza Tavakkoli

SKMC Student Presentations and Publications

Spaceflight associated neuro-ocular syndrome (SANS) is one of the largest physiologic barriers to spaceflight and requires evaluation and mitigation for future planetary missions. As the spaceflight environment is a clinically limited environment, the purpose of this research is to provide automated, early detection and prognosis of SANS with a machine learning model trained and validated on astronaut SANS optical coherence tomography (OCT) images. In this study, we present a lightweight convolutional neural network (CNN) incorporating an EfficientNet encoder for detecting SANS from OCT images titled "SANS-CNN." We used 6303 OCT B-scan images for training/validation (80%/20% split) and 945 for testing …

A Therapeutically Targetable Positive Feedback Loop Between Nc-Hlx-2-7, Hlx, And Myc That Promotes Group 3 Medulloblastoma, Keisuke Katsushima, Kandarp Joshi, Menglang Yuan, Brigette Romero, Mona Batish, Stacie Stapleton, George Jallo, Elayaraja Kolanthai, Sudipta Seal, Olivier Saulnier, Michael D Taylor, Robert J Wechsler-Reya, Charles G Eberhart, Ranjan J Perera

Faculty, Staff and Students Publications

Recent studies suggest that long non-coding RNAs (lncRNAs) contribute to medulloblastoma (MB) formation and progression. We have identified an lncRNA, lnc-HLX-2-7, as a potential therapeutic target in group 3 (G3) MBs. lnc-HLX-2-7 RNA specifically accumulates in the promoter region of HLX, a sense-overlapping gene of lnc-HLX-2-7, which activates HLX expression by recruiting multiple factors, including enhancer elements. RNA sequencing and chromatin immunoprecipitation reveal that HLX binds to and activates the promoters of several oncogenes, including TBX2, LIN9, HOXM1, and MYC. Intravenous treatment with cerium-oxide-nanoparticle-coated antisense oligonucleotides targeting lnc-HLX-2-7 (CNP-lnc-HLX-2-7) inhibits tumor growth by 40%-50% in an intracranial MB xenograft mouse …

Dopamine Lesions Alter The Striatal Encoding Of Single-Limb Gait, Long Yang, Deepak Singla, Alexander K Wu, Katy A Cross, Sotiris C Masmanidis

Faculty, Staff and Student Publications

The striatum serves an important role in motor control, and neurons in this area encode the body's initiation, cessation, and speed of locomotion. However, it remains unclear whether the same neurons also encode the step-by-step rhythmic motor patterns of individual limbs that characterize gait. By combining high-speed video tracking, electrophysiology, and optogenetic tagging, we found that a sizable population of both D1 and D2 receptor expressing medium spiny projection neurons (MSNs) were phase-locked to the gait cycle of individual limbs in mice. Healthy animals showed balanced limb phase-locking between D1 and D2 MSNs, while dopamine depletion led to stronger phase-locking …

A Clinical Practice Guideline For The Management Of Patients With Acute Spinal Cord Injury: Recommendations On Hemodynamic Management, Brian K. Kwon, Lindsay A. Tetreault, Allan R. Martin, Paul M. Arnold, Rex A.W. Marco, Virginia F.J Newcombe, Carl M. Zipser, Stephen L. Mckenna, Radha Korupolu, Chris J. Neal, Rajiv Saigal, Nina E. Glass, Sam Douglas, Mario Ganau, Vafa Rahimi-Movaghar, James S. Harrop, Bizhan Aarabi, Jefferson R. Wilson, Nathan Evaniew, Andrea C. Skelly, Michael G. Fehlings

Department of Neurosurgery Faculty Papers

STUDY DESIGN: Clinical practice guideline development following the GRADE process.

OBJECTIVES: Hemodynamic management is one of the only available treatment options that likely improves neurologic outcomes in patients with acute traumatic spinal cord injury (SCI). Augmenting mean arterial pressure (MAP) aims to improve blood perfusion and oxygen delivery to the injured spinal cord in order to minimize secondary ischemic damage to neural tissue. The objective of this guideline was to update the 2013 AANS/CNS recommendations on the hemodynamic management of patients with acute traumatic SCI, acknowledging that much has been published in this area since its publication. Specifically, we sought …

Tmem106b Coding Variant Is Protective And Deletion Detrimental In A Mouse Model Of Tauopathy, George A Edwards, Caleb A Wood, Yang He, Quynh Nguyen, Peter J Kim, Ruben Gomez-Gutierrez, Kyung-Won Park, Yong Xu, Cody Zurhellen, Ismael Al-Ramahi, Joanna L Jankowsky

Duncan NRI Faculty and Staff Publications

TMEM106B is a risk modifier of multiple neurological conditions, where a single coding variant and multiple non-coding SNPs influence the balance between susceptibility and resilience. Two key questions that emerge from past work are whether the lone T185S coding variant contributes to protection, and if the presence of TMEM106B is helpful or harmful in the context of disease. Here, we address both questions while expanding the scope of TMEM106B study from TDP-43 to models of tauopathy. We generated knockout mice with constitutive deletion of TMEM106B, alongside knock-in mice encoding the T186S knock-in mutation (equivalent to the human T185S variant), and …

Advocacy Connection Team-Now Educational Program For Headache Fellows And Patients/Caregivers: Assessment Of Educational Objectives, Courtney Seebadri-White, Hsiangkuo Yuan, William B. Young, Karissa N. Arca

Department of Neurology Faculty Papers

OBJECTIVE: To assess for improvement in comfort in participating in advocacy for migraine and headache disorders and knowledge needed for successful advocacy.

BACKGROUND: The Advocacy Connection Team (ACT)-Now program is an educational program offered through Miles for Migraine, a non-profit advocacy organization. It is designed to teach headache fellows and patients advocacy skills.

METHODS: In a cross-sectional pre-test-post-test design, the 2021 ACT-Now cohort of 98 participants were administered a set of 11 pre-course survey questions identifying their role (healthcare provider/headache fellow or patient/caregiver), baseline knowledge of migraine-related disability and stigma, and baseline engagement and comfort with advocating. The post-course survey …

Influence Of Neurotoxin Load On Parkinson’S Disease Pathophysiology, Abhishekh Pokhrel, Daniel Salinas, Nawaz Hack, Kelsey Potter-Baker

Research Symposium

Background: Parkinson’s disease (PD) is a debilitating neurodegenerative disorder impacting movement, mood, and cognition. Among those affected, veterans, due to their occupational exposures, are particularly susceptible, contributing to over 110,000 PD cases in the United States. Studies have largely attributed this increased prevalence among veterans to environmental neurotoxins such as Agent Orange, MPTP, and 6-OHDA. However, it remains unclear how neurotoxin exposure load influences biological mechanisms in PD. This study aims to elucidate the influence of neurotoxin load on PD-associated molecular changes, neuroplasticity, neurodegeneration, and cognitive and motor function within a clinical population of the Rio Grande Valley region …

Edge-Wise Analysis Reveals White Matter Connectivity Associated With Focal To Bilateral Tonic-Clonic Seizures, Sam S. Javidi, Xiaosong He, Ankeeta Ankeeta, Qirui Zhang, Salvatore Citro, Michael R. Sperling, Joseph I. Tracy

Farber Institute for Neuroscience Faculty Papers

OBJECTIVE: Focal to bilateral tonic-clonic seizures (FBTCS) represent a challenging subtype of focal temporal lobe epilepsy (TLE) in terms of both severity and treatment response. Most studies have focused on regional brain analysis that is agnostic to the distribution of white matter (WM) pathways associated with a node. We implemented a more selective, edge-wise approach that allowed for identification of the individual connections unique to FBTCS.

METHODS: T1-weighted and diffusion-weighted images were obtained from 22 patients with solely focal seizures (FS), 43 FBTCS patients, and 65 age/sex-matched healthy participants (HPs), yielding streamline (STR) connectome matrices. We used diffusion tensor-derived STRs …

Childhood Cancer Mutagenesis Caused By Transposase-Derived Pgbd5, Makiko Yamada, Ross R Keller, Rodrigo Lopez Gutierrez, Daniel Cameron, Hiromichi Suzuki, Reeti Sanghrajka, Jake Vaynshteyn, Jeffrey Gerwin, Francesco Maura, William Hooper, Minita Shah, Nicolas Robine, Phillip Demarest, N Sumru Bayin, Luz Jubierre Zapater, Casie Reed, Steven Hébert, Ignas Masilionis, Ronan Chaligne, Nicholas D Socci, Michael D Taylor, Claudia L Kleinman, Alexandra L Joyner, G Praveen Raju, Alex Kentsis

Faculty, Staff and Students Publications

Genomic rearrangements are a hallmark of most childhood tumors, including medulloblastoma, one of the most common brain tumors in children, but their causes remain largely unknown. Here, we show that PiggyBac transposable element derived 5 (Pgbd5) promotes tumor development in multiple developmentally accurate mouse models of Sonic Hedgehog (SHH) medulloblastoma. Most Pgbd5-deficient mice do not develop tumors, while maintaining normal cerebellar development. Ectopic activation of SHH signaling is sufficient to enforce cerebellar granule cell progenitor-like cell states, which exhibit Pgbd5-dependent expression of distinct DNA repair and neurodevelopmental factors. Mouse medulloblastomas expressing Pgbd5 have increased numbers of somatic structural DNA rearrangements, …

Tumor Treating Fields Suppress Tumor Cell Growth And Neurologic Decline In Models Of Spinal Metastases, Daniel Ledbetter, Romulo Augusto Andrade De Almeida, Xizi Wu, Ariel Naveh, Chirag B Patel, Queena Gonzalez, Thomas H Beckham, Robert North, Laurence Rhines, Jing Li, Amol Ghia, David Aten, Claudio Tatsui, Christopher Alvarez-Breckenridge

Faculty, Staff and Student Publications

Spinal metastases can result in severe neurologic compromise and decreased overall survival. Despite treatment advances, local disease progression is frequent, highlighting the need for novel therapies. Tumor treating fields (TTFields) impair tumor cell replication and are influenced by properties of surrounding tissue. We hypothesized that bone's dielectric properties will enhance TTFields-mediated suppression of tumor growth in spinal metastasis models. Computational modeling of TTFields intensity was performed following surgical resection of a spinal metastasis and demonstrated enhanced TTFields intensity within the resected vertebral body. Additionally, luciferase-tagged human KRIB osteosarcoma and A549 lung adenocarcinoma cell lines were cultured in demineralized bone grafts …

Mapping Sca1 Regional Vulnerabilities Reveals Neural And Skeletal Muscle Contributions To Disease, Lisa Duvick, W Michael Southern, Kellie A Benzow, Zoe N Burch, Hillary P Handler, Jason S Mitchell, Hannah Kuivinen, Udaya Gadiparthi, Praseuth Yang, Alyssa Soles, Carrie A Sheeler, Orion Rainwater, Shannah Serres, Erin B Lind, Tessa Nichols-Meade, Yun You, Brennon O'Callaghan, Huda Y Zoghbi, Marija Cvetanovic, Vanessa C Wheeler, James M Ervasti, Michael D Koob, Harry T Orr

Duncan NRI Faculty and Staff Publications

Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by an expanded polyglutamine tract in the widely expressed ataxin-1 (ATXN1) protein. To elucidate anatomical regions and cell types that underlie mutant ATXN1-induced disease phenotypes, we developed a floxed conditional knockin mouse (f-ATXN1146Q/2Q) with mouse Atxn1 coding exons replaced by human ATXN1 exons encoding 146 glutamines. f-ATXN1146Q/2Q mice manifested SCA1-like phenotypes including motor and cognitive deficits, wasting, and decreased survival. Central nervous system (CNS) contributions to disease were revealed using f-ATXN1146Q/2Q;Nestin-Cre mice, which showed improved rotarod, open field, and Barnes maze performance by 6-12 weeks of age. In contrast, …

Racial Disparities In The Utilization Of Invasive Neuromodulation Devices For The Treatment Of Drug-Resistant Focal Epilepsy, Juan Luis Alcala-Zermeno, Brandy Fureman, Caitlin L. Grzeskowiak, Ojas Potnis, Maria Taveras, Margaret W. Logan, Delanie Rybacki, Daniel Friedman, Daniel Lowenstein, Ruben Kuzniecky, Jacqueline French, Hep2 Investigators

Student Papers, Posters & Projects

Racial disparities affect multiple dimensions of epilepsy care including epilepsy surgery. This study aims to further explore these disparities by determining the utilization of invasive neuromodulation devices according to race and ethnicity in a multicenter study of patients living with focal drug-resistant epilepsy (DRE). We performed a post hoc analysis of the Human Epilepsy Project 2 (HEP2) data. HEP2 is a prospective study of patients living with focal DRE involving 10 sites distributed across the United States. There were no statistical differences in the racial distribution of the study population compared to the US population using census data except for …

A Tough Bioadhesive Hydrogel Supports Sutureless Sealing Of The Dural Membrane In Porcine And Ex Vivo Human Tissue, Kyle C Wu, Benjamin R Freedman, Phoebe S Kwon, Matthew Torre, Daniel O Kent, Wenya Linda Bi, David J Mooney

Duncan NRI Faculty and Staff Publications

Complete sequestration of central nervous system tissue and cerebrospinal fluid by the dural membrane is fundamental to maintaining homeostasis and proper organ function, making reconstruction of this layer an essential step during neurosurgery. Primary closure of the dura by suture repair is the current standard, despite facing technical, microenvironmental, and anatomic challenges. Here, we apply a mechanically tough hydrogel paired with a bioadhesive for intraoperative sealing of the dural membrane in rodent, porcine, and human central nervous system tissue. Tensile testing demonstrated that this dural tough adhesive (DTA) exhibited greater toughness with higher maximum stress and stretch compared with commercial …

The Influence Of Computerized Tomography Imaging On Treatment Of Periprosthetic Proximal Femur Fractures, Gill Gilworth, Katherine Harris, Toby L Morgan, Salma Ayis, Julia Fox-Rushby, Emma Godfrey, Nicholas S Hopkinson, Simon Lewin, Ka Keat Lim, Arietta Spinou, Stephanie J C Taylor, Patrick White

Faculty, Staff and Student Publications

Background

Pulmonary rehabilitation (PR) is a programme of exercise and education and the most effective treatment for the symptoms and disability associated with chronic obstructive pulmonary disease. However, the benefits of PR are limited by poor uptake and completion. This trial will determine whether using trained volunteer lay health workers, called “PR buddies,” improves uptake and completion of PR and is cost-effective. This trial protocol outlines the methods for evaluating effectiveness, cost-effectiveness, and acceptability.

Methods

The IMPROVE trial is a pragmatic, open, cluster randomised controlled trial planned in 38 PR services across England and Wales. PR services will be randomised …

Most Recent Advances And Applications Of Extracellular Vesicles In Tackling Neurological Challenges, Mandeep Kaur, Salvatore Fusco, Bram Van Den Broek, Jaya Aseervatham, Abdolmohamad Rostami, Lorraine Iacovitti, Claudio Grassi, Barbara Lukomska, Amit K. Srivastava

Cardeza Foundation for Hematologic Research

Over the past few decades, there has been a notable increase in the global burden of central nervous system (CNS) diseases. Despite advances in technology and therapeutic options, neurological and neurodegenerative disorders persist as significant challenges in treatment and cure. Recently, there has been a remarkable surge of interest in extracellular vesicles (EVs) as pivotal mediators of intercellular communication. As carriers of molecular cargo, EVs demonstrate the ability to traverse the blood-brain barrier, enabling bidirectional communication. As a result, they have garnered attention as potential biomarkers and therapeutic agents, whether in their natural form or after being engineered for use …