Neurology Commons^™

Arterial Spin Labeling Changes Parallel Asymmetric Perisylvian And Perirolandic Symptoms In 3 Pediatric Cases Of Anti-Nmdar Encephalitis, Alexander J Sandweiss, Varun Kannan, Nilesh K Desai, Stephen F Kralik, Eyal Muscal, Kristen S Fisher

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: Anti-NMDA receptor autoimmune encephalitis (NMDAR AE) is an autoantibody-mediated disorder characterized by seizures, neuropsychiatric symptoms, movement disorder, and focal neurologic deficits. Conventionally defined broadly as an inflammatory brain disease, the heterotopic localization is rarely discussed in children. Imaging findings are often nonspecific, and there are no early biomarkers of disease other than the presence of anti-NMDAR antibodies.

METHODS: We conducted a retrospective analysis of our pediatric NMDAR AE cases (as determined by either positive serum or CSF antibodies or both) at Texas Children's Hospital between 2020-2021 and extracted medical record data of those patients who had arterial …

Telehealth For Assessing And Managing Tardive Dyskinesia: Expert Insights From A Cross-Disciplinary Virtual Treatment Panel, Rif S El-Mallakh, Amy Belnap, Sanjay Iyer, Jeremy Schreiber, Desiree Matthews, Linda Lefler, Daniel Dees, Allen Bott, Nora Vanegas-Arroyave, Adam Wolff, Ulises Pesce, Khody Farahmand, Chirag Shah, Leslie Lundt

Faculty, Staff and Students Publications

Introduction: Publications on the integration of telehealth in the care of patients with movement disorders are increasing, but little has been presented regarding its use in tardive dyskinesia (TD), a drug-induced movement disorder associated with prolonged exposure to dopamine receptor blocking agents. This study was conducted to address that knowledge gap, based on insights from a panel of TD experts.

Methods: In 2020, six neurologists, three psychiatrists, and three psychiatric nurse practitioners participated in individual semistructured interviews about in-person and virtual TD assessment and management in their practices. Two virtual roundtables were then conducted to consolidate findings from these interviews. …

Treatment Of Cervical Dystonia With Botox (Onabotulinumtoxina): Development, Insights, And Impact, Joseph Jankovic, Joseph Tsui, Mitchell F Brin

Faculty, Staff and Students Publications

Cervical dystonia (CD), the most common focal dystonia encountered in neurologic practice, is a chronic disorder in which the muscles of the neck involuntarily contract and cause abnormal postures and movements of the head, neck, and shoulders. Treatment of CD prior to botulinum toxin was unsatisfactory, as existing therapies often did not improve symptoms. The use of botulinum toxin for CD grew out of its success in treating blepharospasm, another type of focal dystonia. On the basis of results from a double-blind, placebo-controlled trial, onabotulinumtoxinA was approved in 2000 in the US for the treatment of CD in adults in …

Contrasting Features Between Tourette Syndrome And Secondary Tic Disorders, José Fidel Baizabal-Carvallo, Marlene Alonso-Juarez, Joseph Jankovic

Faculty, Staff and Students Publications

Tics are rapid, recurrent, non-rhythmic movements or emitted sounds. Tics are the hallmark of Tourette syndrome (TS); however, a number of other disorders may be associated with tics, so-called secondary tic disorders (STD). We assessed clinical history and performed blinded evaluations of video-recordings from patients with TS and STD in order to identify features that may differentiate tics associated with TS vs STD. There were 156 patients with TS and 38 with STD, 21 of whom had functional (psychogenic) tics. Patients with TS were more frequently male and had a younger age at onset. Tics in TS tend to involve …

Discriminating Mild Traumatic Brain Injury And Posttraumatic Stress Disorder Using Latent Neuroimaging And Neuropsychological Profiles In Active-Duty Military Service Members, Nicola L De Souza, Carrie Esopenko, Yuane Jia, J Scott Parrott, Tricia L Merkley, Emily L Dennis, Frank G Hillary, Carmen Velez, Douglas B Cooper, Jan E Kennedy, Jeffrey D Lewis, Gerald E York, Deleene S Menefee, Stephen R Mccauley, Amy O Bowles, Elisabeth A Wilde, David F Tate

Faculty, Staff and Students Publications

OBJECTIVE: Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) commonly occur among military Service Members and Veterans and have heterogenous, but also overlapping symptom presentations, which often complicate the diagnoses of underlying impairments and development of effective treatment plans. Thus, we sought to examine whether the combination of whole brain gray matter (GM) and white matter (WM) structural measures with neuropsychological performance can aid in the classification of military personnel with mTBI and PTSD.

METHODS: Active-Duty US Service Members ( n = 156; 87.8% male) with a history of mTBI, PTSD, combined mTBI+PTSD, or orthopedic injury completed a …

Poly(A)-Binding Protein Is An Ataxin-2 Chaperone That Regulates Biomolecular Condensates, Steven Boeynaems, Yanniv Dorone, Yanrong Zhuang, Victoria Shabardina, Guozhong Huang, Anca Marian, Garam Kim, Anushka Sanyal, Nesli-Ece Şen, Daniel Griffith, Roberto Docampo, Keren Lasker, Iñaki Ruiz-Trillo, Georg Auburger, Alex S Holehouse, Edor Kabashi, Yi Lin, Aaron D Gitler

Duncan NRI Faculty and Staff Publications

Biomolecular condensation underlies the biogenesis of an expanding array of membraneless assemblies, including stress granules (SGs) which form under a variety of cellular stresses. Advances have been made in understanding the molecular grammar of a few scaffold proteins that make up these phases, but how the partitioning of hundreds of SG proteins is regulated remains largely unresolved. While investigating the rules that govern the condensation of ataxin-2, a SG protein implicated in neurodegenerative disease, we unexpectedly identified a short 14aa sequence that acts as a condensation switch and is conserved across the eukaryote lineage. We identify poly(A)-binding proteins as unconventional …

A Novel Comorbidity Score For Older Adults With Non-Hodgkin Lymphoma: The 3-Factor Risk Estimate Scale, Max J Gordon, Zhigang Duan, Hui Zhao, Loretta Nastoupil, Alessandra Ferrajoli, Alexey V Danilov, Sharon H Giordano

Faculty, Staff and Student Publications

For patients with non-Hodgkin lymphoma (NHL), formal comorbidity assessment is recommended but is rarely conducted in routine practice. A simple, validated measure of comorbidities that standardizes their assessment could improve adherence to guidelines. We previously constructed the 3-factor risk estimate scale (TRES) among patients with chronic lymphocytic leukemia (CLL). Here, we investigated TRES in multiple NHL subtypes. In the surveillance, epidemiology, and end results-Medicare database, patients with NHL diagnosed from 2008 to 2017 were included. Upper gastrointestinal, endocrine, and vascular comorbidities were identified using ICD-9/ICD-10 codes to assign TRES scores. Patient characteristic distributions were compared using χ2 or t test. …

Biological Mechanism Of Sex Difference In Stroke Manifestation And Outcomes, Wi-Sun Ryu, Jinyong Chung, Dawid Schellingerhout, Sang-Wuk Jeong, Hang-Rai Kim, Jung E Park, Beom Joon Kim, Joon-Tae Kim, Keun-Sik Hong, Kyungbok Lee, Tai Hwan Park, Sang-Soon Park, Jong-Moo Park, Kyusik Kang, Yong-Jin Cho, Hong-Kyun Park, Byung-Chul Lee, Kyung-Ho Yu, Mi Sun Oh, Soo Joo Lee, Jae Guk Kim, Jae-Kwan Cha, Dae-Hyun Kim, Jun Lee, Moon-Ku Han, Man Seok Park, Kang-Ho Choi, Juneyoung Lee, Hee-Joon Bae, Dong-Eog Kim

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Female patients tend to have greater disability and worse long-term outcomes after stroke than male patients. To date, the biological basis of sex difference in ischemic stroke remains unclear. We aimed to (1) assess sex differences in clinical manifestation and outcomes of acute ischemic stroke and (2) investigate whether the sex disparity is due to different infarct locations or different impacts of infarct in the same location.

METHODS: This MRI-based multicenter study included 6,464 consecutive patients with acute ischemic stroke (<7 >days) from 11 centers in South Korea (May 2011-January 2013). Multivariable statistical and brain mapping methods …

Neurocognitive Dysfunction With Neuronal Injury In People With Hiv On Long-Duration Antiretroviral Therapy, Cynthia Mcmahan, Devon K Dietrich, Elizabeth F Horne, Erin Kelly, Katrina Geannopoulos, Peter Selim Siyahhan Julnes, Lillian Ham, Ulisses Santamaria, Chuen-Yen Lau, Tianxia Wu, Hsing-Chuan Hsieh, Anuradha Ganesan, Catherine Berjohn, Suad Kapetanovic, Daniel S Reich, Govind Nair, Joseph Snow, Brian K Agan, Avindra Nath, Bryan R Smith

Staff and Researcher Publications

Background and objectives: Neurologic outcomes in people with HIV (PWH) on long-duration antiretroviral therapy (ART) are not fully understood, and the underlying pathophysiology is unclear. To address this, we established a cohort of such individuals and compared them with HIV-negative controls using a novel matching technique. Both groups underwent extensive cognitive testing, evaluation for psychiatric measures, and MRI and CSF analyses.

Methods: Participants underwent comprehensive neuropsychological testing and completed standardized questionnaires measuring depressive symptoms, perceptions of own functioning, and activities of daily living as part of an observational study. Brain MRI and lumbar puncture were optional. Coarsened Exact Matching was …

Effects Of Spaceflight On The Eeg Alpha Power And Functional Connectivity, Sandra Pusil, Jonathan Zegarra-Valdivia, Pablo Cuesta, Christopher Laohathai, Ana Maria Cebolla, Jens Haueisen, Patrique Fiedler, Michael Funke, Fernando Maestú, Guy Cheron

Faculty, Staff and Student Publications

Electroencephalography (EEG) can detect changes in cerebral activity during spaceflight. This study evaluates the effect of spaceflight on brain networks through analysis of the Default Mode Network (DMN)'s alpha frequency band power and functional connectivity (FC), and the persistence of these changes. Five astronauts' resting state EEGs under three conditions were analyzed (pre-flight, in-flight, and post-flight). DMN's alpha band power and FC were computed using eLORETA and phase-locking value. Eyes-opened (EO) and eyes-closed (EC) conditions were differentiated. We found a DMN alpha band power reduction during in-flight (EC: p < 0.001; EO: p < 0.05) and post-flight (EC: p < 0.001; EO: p < 0.01) when compared to pre-flight condition. FC strength decreased during in-flight (EC: p < 0.01; EO: p < 0.01) and post-flight (EC: ns; EO: p < 0.01) compared to pre-flight condition. The DMN alpha band power and FC strength reduction persisted until 20 days after landing. Spaceflight caused electrocerebral alterations that persisted after return to earth. Periodic assessment by EEG-derived DMN analysis has the potential to become a neurophysiologic marker of cerebral functional integrity during exploration missions to space.

Vagus Nerve Stimulation Paired With Rehabilitation For Upper Limb Motor Impairment And Function After Chronic Ischemic Stroke: Subgroup Analysis Of The Randomized, Blinded, Pivotal, Vns-Rehab Device Trial, Jesse Dawson, Navzer D Engineer, Steven C Cramer, Steven L Wolf, Rushna Ali, Michael W O'Dell, David Pierce, Cecília N Prudente, Jessica Redgrave, Wuwei Feng, Charles Y Liu, Gerard E Francisco, Benjamin L Brown, Anand Dixit, Jen Alexander, Louis Demark, Vibor Krishna, Steven A Kautz, Arshad Majid, Brent Tarver, Duncan L Turner, Teresa J Kimberley

Faculty, Staff and Student Publications

BACKGROUND: Vagus Nerve Stimulation (VNS) paired with rehabilitation improved upper extremity impairment and function in a recent pivotal, randomized, triple-blind, sham-controlled trial in people with chronic arm weakness after stroke.

OBJECTIVE: We aimed to determine whether treatment effects varied across candidate subgroups, such as younger age or less injury.

METHODS: Participants were randomized to receive rehabilitation paired with active VNS or rehabilitation paired with sham stimulation (Control). The primary outcome was the change in impairment measured by the Fugl-Meyer Assessment Upper Extremity (FMA-UE) score on the first day after completion of 6-weeks in-clinic therapy. We explored the effect of VNS …

The Tempo And Mode Of Gene Regulatory Programs During Bacterial Infection, Rocio Diaz Escarcega, Abhijeet A Patil, Matthew D Meyer, Jose F Moruno-Manchon, Alexander D Silvagnoli, Louise D Mccullough, Andrey S Tsvetkov

Faculty, Staff and Student Publications

Tardigrades are microscopic invertebrates, which are capable of withstanding extreme environmental conditions, including high levels of radiation. A Tardigrade protein, Dsup (Damage Suppressor), protects the Tardigrade's DNA during harsh environmental stress and X-rays. When expressed in cancer cells, Dsup protects DNA from single- and double-strand breaks (DSBs) induced by radiation, increases survival of irradiated cells, and protects DNA from reactive oxygen species. These unusual properties of Dsup suggested that understanding how the protein functions may help in the design of small molecules that could protect humans during radiotherapy or space travel. Here, we investigated if Dsup is protective in cortical …

Role Of The Meningeal Lymphatics In Stroke, Maharajni Perla, Viola Caretti, María A Moro, Louise D Mccullough

Faculty, Staff and Student Publications

No abstract provided.

Sex And Gender Differences In Acute Stroke Care: Metrics, Access To Treatment And Outcome A Territorial Analysis Of The Stroke Code System Of Catalonia, Yolanda Silva, Laura Sánchez-Cirera, Mikel Terceño, Laura Dorado, Adrián Valls, Marina Martínez, Sònia Abilleira, Marta Rubiera, Helena Quesada, Laura Llull, Ana Rodríguez-Campello, Joan Martí-Fàbregas, Laia Seró, Francisco Purroy, Iago Payo, Sònia García, David Cánovas, Jurek Krupinski, Natalia Mas, Ernest Palomeras, Dolores Cocho, Maria Àngels Font, Esther Catena, Elsa Puiggròs, Claudia Pedroza, Gemma Marín, Dolors Carrión, Xavier Costa, Mari Cruz Almendros, Ivan Torres, Carla Colom, John Alejandro Velasquez, Gloria Diaz, Xavier Jiménez, Teresa Subirats, Anna Deulofeu, Verónica Hidalgo, Mercè Salvat-Plana, Natalia Pérez De La Ossa, Catalan Stroke Code And Reperfusion Consortium (Cat-Scr)

Faculty, Staff and Student Publications

INTRODUCTION: Previous studies have reported differences in the management and outcome of women stroke patients in comparison with men. We aim to analyze sex and gender differences in the medical assistance, access to treatment and outcome of acute stroke patients in Catalonia.

PATIENTS AND METHODS: Data were obtained from a prospective population-based registry of stroke code activations in Catalonia (CICAT) from January/2016 to December/2019. The registry includes demographic data, stroke severity, stroke subtype, reperfusion therapy, and time workflow. Centralized clinical outcome at 90 days was assessed in patients receiving reperfusion therapy.

RESULTS: A total of 23,371 stroke code activations were …

Dual-Target Deep Brain Stimulation For Obsessive-Compulsive Disorder And Tourette Syndrome, Ricardo A Najera, Nicole Provenza, Huy Dang, Kalman A Katlowitz, Alyssa Hertz, Sandesh Reddy, Ben Shofty, Steven T Bellows, Eric A Storch, Wayne K Goodman, Sameer A Sheth

Faculty, Staff and Students Publications

No abstract provided.

Imaging Of Pediatric Calvarial And Skull Base Tumors: A Cog Diagnostic Imaging Committee/Spr Oncology Committee/Asnpr White Paper, Jarunee Intrapiromkul, Pattana Wangaryattawanich, Zoltan Patay, Thierry A G M Huisman, Jason N Wright, Jeremy Y Jones, Raghu Ramakrishnaiah, Rajan Patel, Adam E Goldman-Yassen, Stephen Kralik, Mark Mamlouk, Nilesh K Desai

Faculty, Staff and Students Publications

A standardized imaging protocol for pediatric oncology patients is essential for accurate and efficient imaging, while simultaneously promoting collaborative understanding of pathologies and radiologic assessment of treatment response. The objective of this article is to provide standardized pediatric imaging guidelines and parameters for evaluation of tumors of the pediatric orbit, calvarium, skull base, and temporal bone. This article was drafted based on current scientific literature as well as consensus opinions of imaging experts in collaboration with the Children's Oncology Group Diagnostic Imaging Committee, Society of Pediatric Radiology Oncology Committee, and American Society of Pediatric Neuroradiology.

Declining Autozygosity Over Time: An Exploration In Over 1 Million Individuals From Three Diverse Cohorts, Sarah M C Colbert, Frank R Wendt, Gita A Pathak, Drew A Helmer, Elizabeth R Hauser, Matthew C Keller, Renato Polimanti, Emma C Johnson

Faculty, Staff and Students Publications

Previous studies have hypothesized that autozygosity is decreasing over generational time. However, these studies were limited to relatively small samples (n < 11,000) lacking in diversity, which may limit the generalizability of their findings. We present data that partially support this hypothesis from three large cohorts of diverse ancestries, two from the US (All of Us, n = 82,474; the Million Veteran Program, n = 622,497) and one from the UK (UK Biobank, n = 380,899). Our results from a mixed-effect meta-analysis demonstrate an overall trend of decreasing autozygosity over generational time (meta-analyzed slope = -0.029, SE = 0.009, p = 6.03e-4). On the basis of our estimates, we would predict F

Thirty-Day Outcomes Of Resolute Onyx Stent For Symptomatic Intracranial Stenosis: A Multicenter Propensity Score-Matched Comparison With Stenting Versus Aggressive Medical Management For Preventing Recurrent Stroke In Intracranial Stenosis Trial, Farhan Siddiq, Ravi S Nunna, Jonathan M Beall, Inamullah Khan, Musharaf Khan, Wondwossen G Tekle, Mohamad Ezzeldin, Omar Tanweer, Jan-Karl Burkhardt, Pascal M Jabbour, Stavropoula I Tjoumakaris, Nabeel A Herial, Adnan H Siddiqui, Ramesh Grandhi, Renee L Martin, Adnan I Qureshi, Ameer E Hassan

Faculty, Staff and Students Publications

BACKGROUND: Symptomatic intracranial atherosclerotic disease (sICAD) is estimated to cause 10% of strokes annually in the United States. However, treatment remains a challenge with several different stenting options studied in the past with unfavorable results.

OBJECTIVE: To report the 30-day stroke and/or death rate associated with intracranial stent placement for sICAD using Resolute Onyx Zotarolimus-Eluting Stent (RO-ZES) and provide a comparison with the results of Stenting Versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial.

METHODS: Prospectively maintained databases across 8 stroke centers were used to identify adult patients treated with RO-ZES for sICAD between January …

Imaging Of Pediatric Cardiac Tumors: A Cog Diagnostic Imaging Committee/Spr Oncology Committee White Paper, Cara E Morin, Lindsay M Griffin, Rebecca S Beroukhim, Pablo Caro-Domínguez, Sherwin Chan, Jason N Johnson, Juan C Infante, Christopher Z Lam, Ladonna J Malone, Elizabeth R Tang, Michael D Taylor, James C Wilkinson, Prakash M Masand

Faculty, Staff and Students Publications

Cardiac tumors in children are rare and the majority are benign. The most common cardiac tumor in children is rhabdomyoma, usually associated with tuberous sclerosis complex. Other benign cardiac masses include fibromas, myxomas, hemangiomas, and teratomas. Primary malignant cardiac tumors are exceedingly rare, with the most common pathology being soft tissue sarcomas. This paper provides consensus-based imaging recommendations for the evaluation of patients with cardiac tumors at diagnosis and follow-up, including during and after therapy.

Actigraphic Correlates Of Neuropsychiatric Symptoms In Adults With Focal Epilepsy, Mark A Abboud, Jessica L Kamen, John S Bass, Lu Lin, Jay R Gavvala, Sindhu Rao, Stephen F Smagula, Vaishnav Krishnan

Faculty, Staff and Student Publications

Objectives:

Disability in patients with epilepsy (PWEs) is multifactorial: beyond seizure frequency/severity, PWEs are prone to a range of neuropsychiatric, cognitive, and somatic comorbidities that significantly affect quality of life. Here, we explored how variations in seizure severity and the burden of self-reported somatic/neuropsychiatric symptoms correlate with disruptions to 24 h activity patterns (rest-activity rhythms [RARs]), determined through wrist accelerometry/actigraphy.

Methods:

Multiday wrist-actigraphy recordings were obtained from 59 adult patients with focal epilepsy (44% male, ages 18–72), who contemporaneously responded to validated psychometric instruments to measure anxiety, depression, sleepiness, and somatic symptoms. We conducted a similar in silico psychometric-actigraphic correlation …

De Novo Variants In Mrtfb Have Gain-Of-Function Activity In Drosophila And Are Associated With A Novel Neurodevelopmental Phenotype With Dysmorphic Features, Jonathan C Andrews, Jung-Wan Mok, Oguz Kanca, Sharayu Jangam, Cynthia Tifft, Ellen F Macnamara, Bianca E Russell, Lee-Kai Wang, Undiagnosed Diseases Network, Stanley F Nelson, Hugo J Bellen, Shinya Yamamoto, May Christine V Malicdan, Michael F Wangler

Duncan NRI Faculty and Staff Publications

Purpose: Myocardin-related transcription factor B (MRTFB) is an important transcriptional regulator, which promotes the activity of an estimated 300 genes but is not known to underlie a Mendelian disorder.

Methods: Probands were identified through the efforts of the Undiagnosed Disease Network. Because the MRTFB protein is highly conserved between vertebrate and invertebrate model organisms, we generated a humanized Drosophila model expressing the human MRTFB protein in the same spatial and temporal pattern as the fly gene. Actin binding assays were used to validate the effect of the variants on MRTFB.

Results: Here, we report 2 pediatric probands with de novo …

Implication Of Chromosomal Microarray Analysis Prior To In-Utero Repair Of Fetal Open Neural Tube Defect, R Zemet, E Krispin, R M Johnson, N R Kumar, L E Westerfield, S Stover, D G Mann, J Castillo, H A Castillo, A A Nassr, M Sanz Cortes, R Donepudi, J Espinoza, W E Whitehead, M A Belfort, A A Shamshirsaz, I B Van Den Veyver

Duncan NRI Faculty and Staff Publications

Objective: In-utero repair of open neural tube defects (ONTD) is an accepted treatment option with demonstrated superior outcome for eligible patients. While current guidelines recommend genetic testing by chromosomal microarray analysis (CMA) when a major congenital anomaly is detected prenatally, the requirement for an in-utero repair, based on the Management of Myelomeningocele Study (MOMS) criteria, is a normal karyotype. In this study, we aimed to evaluate if CMA should be recommended as a prerequisite for in-utero ONTD repair.

Methods: This was a retrospective cohort study of pregnancies complicated by ONTD that underwent laparotomy-assisted fetoscopic repair or open-hysterotomy fetal surgery at …

Glial Progenitor Heterogeneity And Key Regulators Revealed By Single-Cell Rna Sequencing Provide Insight To Regeneration In Spinal Cord Injury, Haichao Wei, Xizi Wu, Joseph Withrow, Raquel Cuevas-Diaz Duran, Simranjit Singh, Lesley S Chaboub, Jyotirmoy Rakshit, Julio Mejia, Andrew Rolfe, Juan J Herrera, Philip J Horner, Jia Qian Wu

Faculty, Staff and Student Publications

Recent studies have revealed the heterogeneous nature of astrocytes; however, how diverse constituents of astrocyte-lineage cells are regulated in adult spinal cord after injury and contribute to regeneration remains elusive. We perform single-cell RNA sequencing of GFAP-expressing cells from sub-chronic spinal cord injury models and identify and compare with the subpopulations in acute-stage data. We find subpopulations with distinct functional enrichment and their identities defined by subpopulation-specific transcription factors and regulons. Immunohistochemistry, RNAscope experiments, and quantification by stereology verify the molecular signature, location, and morphology of potential resident neural progenitors or neural stem cells in the adult spinal cord before …

The Role Of Extracellular Heat Shock Proteins In Cardiovascular Diseases, Soumya Patnaik, Sriram Nathan, Biswajit Kar, Igor D Gregoric, Yi-Ping Li

Faculty, Staff and Student Publications

In the early 1960s, heat shock proteins (HSPs) were first identified as vital intracellular proteinaceous components that help in stress physiology and reprogram the cellular responses to enable the organism's survival. By the early 1990s, HSPs were detected in extracellular spaces and found to activate gamma-delta T-lymphocytes. Subsequent investigations identified their association with varied disease conditions, including autoimmune disorders, diabetes, cancer, hepatic, pancreatic, and renal disorders, and cachexia. In cardiology, extracellular HSPs play a definite, but still unclear, role in atherosclerosis, acute coronary syndromes, and heart failure. The possibility of HSP-targeted novel molecular therapeutics has generated much interest and hope …

Connecting Circuits With Networks In Addiction Neuroscience: A Salience Network Perspective, Adriana K Cushnie, Wei Tang, Sarah R Heilbronner

Faculty, Staff and Students Publications

Human neuroimaging has demonstrated the existence of large-scale functional networks in the cerebral cortex consisting of topographically distant brain regions with functionally correlated activity. The salience network (SN), which is involved in detecting salient stimuli and mediating inter-network communication, is a crucial functional network that is disrupted in addiction. Individuals with addiction display dysfunctional structural and functional connectivity of the SN. Furthermore, while there is a growing body of evidence regarding the SN, addiction, and the relationship between the two, there are still many unknowns, and there are fundamental limitations to human neuroimaging studies. At the same time, advances in …

Neutralizing Antibody Formation With Onabotulinumtoxina (Botox®) Treatment From Global Registration Studies Across Multiple Indications: A Meta-Analysis, Joseph Jankovic, Jean Carruthers, Markus Naumann, Patricia Ogilvie, Terry Boodhoo, Mayssa Attar, Swati Gupta, Ritu Singh, John Soliman, Irina Yushmanova, Mitchell F Brin, Jie Shen

Faculty, Staff and Students Publications

Though the formation of neutralizing antibodies (NAbs) during treatment with botulinum neurotoxin is rare, their presence may nonetheless affect the biological activity of botulinum toxin and negatively impact clinical response. The goal of this updated meta-analysis was to evaluate and characterize the rate of NAb formation using an expanded dataset composed of 33 prospective placebo-controlled and open-label clinical trials with nearly 30,000 longitudinal subject records prior to and following onabotulinumtoxinA treatment in 10 therapeutic and aesthetic indications. Total onabotulinumtoxinA doses per treatment ranged from 10 U to 600 U administered in ≤15 treatment cycles. The NAb formation at baseline and …

Association Of Brain Age, Lesion Volume, And Functional Outcome In Patients With Stroke, Sook-Lei Liew, Nicolas Schweighofer, James H. Cole, Artemis Zavaliangos-Petropulu, Bethany P. Lo, Laura K.M. Han, Tim Hahn, Lianne Schmaal, Miranda R. Donnelly, Jessica N. Jeong, Zhizhuo Wang, Aisha Abdullah, Jun H. Kim, Alexandre Hutton, Giuseppe Barisano, Michael R. Borich, Lara A. Boyd, Amy Brodtmann, Cathrin M. Buetefisch, Winston D. Byblow, Jessica M. Cassidy, Charalambos C. Charalambous, Valentina Ciullo, Adriana Bastos Conforto, Rosalia Dacosta-Aguayo, Julie A. Dicarlo, Martin Domin, Adrienne N. Dula, Natalia Egorova-Brumley, Wuwei Feng, Fatemeh Geranmayeh, Chris M. Gregory, Colleen A. Hanlon, Kathryn Hayward, Jess A. Holguin, Brenton Hordacre, Neda Jahanshad, Steven A. Kautz, Mohamed Salah Khlif, Hosung Kim, Amy Kuceyeski, David J. Lin, Jingchun Liu, Martin Lotze, Bradley J. Macintosh, John L. Margetis, Maria Mataro, Feroze B. Mohamed, Emily R. Olafson, Gilsoon Park, Fabrizio Piras, Kate P. Revill, Pamela Roberts, Andrew D. Robertson, Nerses Sanossian, Heidi M. Schambra, Na Jin Seo, Surjo R. Soekadar, Gianfranco Spalletta, Cathy M. Stinear, Myriam Taga, Wai Kwong Tang, Greg T. Thielman, Daniela Vecchio, Nick S. Ward, Lars T. Westlye, Carolee J. Winstein, George F. Wittenberg, Steven L. Wolf, Kristin A. Wong, Chunshui Yu, Steven C. Cramer, Paul M. Thompson

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. In this study, we examined the impact of brain age, a measure of neurobiological aging derived from whole-brain structural neuroimaging, on poststroke outcomes, with a focus on sensorimotor performance. We hypothesized that more lesion damage would result in older brain age, which would in turn be associated with poorer outcomes. Related, we expected that brain age would mediate the relationship between lesion damage and outcomes. Finally, we hypothesized that structural brain resilience, which we define in …

Surgeons’ Knowledge Regarding Perioperative Pain Management In Patients With Opioid Use Disorder: A Survey Among 260 Members Of The American College Of Surgeons, Caroline E Crocker, Romana Sharmeen, Thu T Tran, Amir M Khan, Wen Li, Joseph L Alcorn

Faculty, Staff and Student Publications

Surfactant protein A (SP-A) has important roles in innate immunity and modulation of pulmonary and extrapulmonary inflammation. Given SP-A has been detected in rat and human brain, we sought to determine if SP-A has a role in modulating inflammation in the neonatal mouse brain. Neonatal wildtype (WT) and SP-A-deficient (SP-A

Ragd Auto-Activating Mutations Impair Mit/Tfe Activity In Kidney Tubulopathy And Cardiomyopathy Syndrome, Irene Sambri, Marco Ferniani, Giulia Campostrini, Marialuisa Testa, Viviana Meraviglia, Mariana E G De Araujo, Ladislav Dokládal, Claudia Vilardo, Jlenia Monfregola, Nicolina Zampelli, Francesca Del Vecchio Blanco, Annalaura Torella, Carolina Ruosi, Simona Fecarotta, Giancarlo Parenti, Leopoldo Staiano, Milena Bellin, Lukas A Huber, Claudio De Virgilio, Francesco Trepiccione, Vincenzo Nigro, Andrea Ballabio

Duncan NRI Faculty and Staff Publications

Heterozygous mutations in the gene encoding RagD GTPase were shown to cause a novel autosomal dominant condition characterized by kidney tubulopathy and cardiomyopathy. We previously demonstrated that RagD, and its paralogue RagC, mediate a non-canonical mTORC1 signaling pathway that inhibits the activity of TFEB and TFE3, transcription factors of the MiT/TFE family and master regulators of lysosomal biogenesis and autophagy. Here we show that RagD mutations causing kidney tubulopathy and cardiomyopathy are "auto- activating", even in the absence of Folliculin, the GAP responsible for RagC/D activation, and cause constitutive phosphorylation of TFEB and TFE3 by mTORC1, without affecting the phosphorylation …

Efficient Cancer Modeling Through Crispr-Cas9/Hdr-Based Somatic Precision Gene Editing In Mice, Wen Bu, Chad J Creighton, Kelsey S Heavener, Carolina Gutierrez, Yongchao Dou, Amy T Ku, Yiqun Zhang, Weiyu Jiang, Jazmin Urrutia, Wen Jiang, Fei Yue, Luyu Jia, Ahmed Atef Ibrahim, Bing Zhang, Shixia Huang, Yi Li

Faculty, Staff and Student Publications

CRISPR-Cas9 has been used successfully to introduce indels in somatic cells of rodents; however, precise editing of single nucleotides has been hampered by limitations of flexibility and efficiency. Here, we report technological modifications to the CRISPR-Cas9 vector system that now allows homology-directed repair-mediated precise editing of any proto-oncogene in murine somatic tissues to generate tumor models with high flexibility and efficiency. Somatic editing of either