Neurology Commons^™

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 …

The Dementia Care Study (D-Care): Recruitment Strategies And Demographic Characteristics Of Participants In A Pragmatic Randomized Trial Of Dementia Care, Mia Yang, Rafael Samper-Ternent, Elena Volpi, Aval-Na'ree Green, Maya Lichtenstein, Katy Araujo, Pamela Borek, Peter Charpentier, James Dziura, Thomas M Gill, Rebecca Galloway, Erich J Greene, Kristin Lenoir, Peter Peduzzi, Can Meng, Jordan Reese, Amy Shelton, Eleni A Skokos, Jenny Summapund, Erin Unger, David B Reuben, Jeff D Williamson, Alan B Stevens

Faculty, Staff and Student Publications

INTRODUCTION: Pragmatic research studies that include diverse dyads of persons living with dementia (PLWD) and their family caregivers are rare.

METHODS: Community-dwelling dyads were recruited for a pragmatic clinical trial evaluating three approaches to dementia care. Four clinical trial sites used shared and site-specific recruitment strategies to enroll health system patients.

RESULTS: Electronic health record (EHR) queries of patients with a diagnosis of dementia and engagement of their clinicians were the main recruitment strategies. A total of 2176 dyads were enrolled, with 80% recruited after the onset of the pandemic. PLWD had a mean age of 80.6 years (SD 8.5), …

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 …

An Exploration Of The Genetics Of The Mutant Huntingtin (Mhtt) Gene In A Cohort Of Patients With Chorea From Different Ethnic Groups In Sub-Saharan Africa, Mendi J. Muthinja, Carlos Othon Guelngar, Maouly Fall, Fatumah Jama, Huda Aldeen Shuja, Jamila Nambafu, Daniel Gams Massi, Oluwadamilola Ojo, Juzar Hooker, Dilraj Sokhi

Internal Medicine, East Africa

Background: Africans are underrepresented in Huntington's disease (HD) research. A European ancestor was postulated to have introduced the mutant Huntingtin (mHtt) gene to the continent; however, recent work has shown the existence of a unique Htt haplotype in South-Africa specific to indigenous Africans.

Objective: We aimed to investigate the CAG trinucleotide repeats expansion in the Htt gene in a geographically diverse cohort of patients with chorea and unaffected controls from sub-Saharan Africa.

Methods: We evaluated 99 participants: 43 patients with chorea, 21 asymptomatic first-degree relatives of subjects with chorea, and 35 healthy controls for the presence of the mHtt. Participants …

Serum Metabolomic Markers Of Protein-Rich Foods And Incident Ckd: Results From The Atherosclerosis Risk In Communities Study, Lauren Bernard, Jingsha Chen, Hyunju Kim, Kari E Wong, Lyn M Steffen, Bing Yu, Eric Boerwinkle, Andrew S Levey, Morgan E Grams, Eugene P Rhee, Casey M Rebholz

Faculty, Staff and Student Publications

RATIONALE & OBJECTIVE: While urine excretion of nitrogen estimates the total protein intake, biomarkers of specific dietary protein sources have been sparsely studied. Using untargeted metabolomics, this study aimed to identify serum metabolomic markers of 6 protein-rich foods and to examine whether dietary protein-related metabolites are associated with incident chronic kidney disease (CKD).

STUDY DESIGN: Prospective cohort study.

SETTING & PARTICIPANTS: A total of 3,726 participants from the Atherosclerosis Risk in Communities study without CKD at baseline.

EXPOSURES: Dietary intake of 6 protein-rich foods (fish, nuts, legumes, red and processed meat, eggs, and poultry), serum metabolites.

OUTCOMES: Incident CKD (estimated …

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 …

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 …

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 …

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)) …

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 …

Final Report Of The Phase Ii Next/Cns-Gct-4 Trial: Gempox Followed By Marrow-Ablative Chemotherapy For Recurrent Intracranial Germ Cell Tumors, Margaret Shatara, Megan Blue, Joseph Stanek, Yin A Liu, Daniel M Prevedello, Pierre Giglio, Vinay K Puduvalli, Sharon L Gardner, Jeffrey C Allen, Kenneth K Wong, Marvin D Nelson, Floyd H Gilles, Roberta H Adams, Jasmine Pauly, Katrina O'Halloran, Ashley S Margol, Girish Dhall, Jonathan L Finlay

Faculty, Staff and Student Publications

Background: Patients with relapsed intracranial germinoma can achieve durable remission with standard chemotherapy regimens and/or reirradiation; however, innovative therapies are required for patients with relapsed and/or refractory intracranial nongerminomatous germ cell tumors (NGGCTs) due to their poor prognosis. Improved outcomes have been reported using reinduction chemotherapy to achieve minimal residual disease, followed by marrow-ablative chemotherapy (HDCx) with autologous hematopoietic progenitor cell rescue (AuHPCR). We conducted a phase II trial evaluating the response and toxicity of a 3-drug combination developed for recurrent intracranial germ cell tumors consisting of gemcitabine, paclitaxel, and oxaliplatin (GemPOx).

Methods: A total of 9 patients with confirmed …

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 …

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 …

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 …