Neurology Commons^™

Electric Field Navigated 1-Hz Rtms For Poststroke Motor Recovery: The E-Fit Randomized Controlled Trial, Dylan J. Edwards, Charle Y. Liu, Kari Dunning, Felipe Fregni, Jarmo Laine, Benjamin E. Leiby, Lynn M. Rogers, Richard L. Harvey

Moss-Magee Rehabilitation Papers

BACKGROUND: To determine if low-frequency repetitive transcranial magnetic stimulation targeting the primary motor cortex contralateral (M1_CL) to the affected corticospinal tract in patients with hemiparetic stroke augments intensive training–related clinical improvement; an extension of the NICHE trial (Navigated Inhibitory rTMS to Contralesional Hemisphere Trial) using an alternative sham coil.

METHODS: The present E-FIT trial (Electric Field Navigated 1Hz rTMS for Post-stroke Motor Recovery Trial) included 5 of 12 NICHE trial outpatient US rehabilitation centers. The stimulation protocol remained identical (1 Hz repetitive transcranial magnetic stimulation, M1_CL, preceding 60-minute therapy, 18 sessions/6 wks; parallel arm randomized clinical …

In Situ Characterization Of 17-4ph Stainless Steel By Small-Angle Neutron Scattering, Shibo Yan, Zijun Wang, Tianfu Li, Zhong Chen, Xiaoming Du, Yuntao Liu, Dongfeng Chen, Kai Sun, Rongdeng Liu, Bing Bai, Xinfu He, Kaitai Liu, Shuanzhu Wang

Faculty, Staff and Student Publications

17-4PH martensitic steel is usually used as valve stems in nuclear power plants and it suffers from thermal aging embrittlement due to long-time service in a high-temperature and high-pressure environment. Here, we characterized the evolution of microstructures at the nano-scale in 17-4PH steel by in situ small-angle neutron scattering (SANS) with a thermo-mechanically coupled loading device. The device could set different temperatures and tensile so that an in situ SANS experiment could dynamically characterize the process of nanoscale structural changes. The results showed that with increasing thermal aging time, the ε-Cu phase precipitates and grows as the temperature is 475 …

Deep Brain Stimulation For Substance Use Disorder: A Systematic Review And Meta-Analysis, Nour Shaheen, Ahmed Shaheen, Can Sarica, Arun Singh, Mario Zanaty, Karim Johari, Andrew Yang, Theresa Zesiewicz, Brian Dalm, Yarema Bezchlibnyk, Andres M Lozano, Oliver Flouty

Department of Neurosurgery Faculty Papers

OBJECTIVE: Substance use disorder (SUD) is a significant public health issue with a high mortality rate. Deep brain stimulation (DBS) has shown promising results in treating SUD in certain cases. In this study, we conducted a meta-analysis to evaluate the efficacy of DBS in the treatment of SUD and reduction of relapse rates.

METHODS: We performed a thorough and methodical search of the existing scientific literature, adhering to the PRISMA guidelines, to identify 16 original studies that fulfilled our inclusion criteria. We used the evidence levels recommended by the Oxford Centre for Evidence-Based Medicine to assess bias. The R version …

Somatic Cell Structural Variant Mutagenesis And Neurologic Disease, James R Lupski

Faculty, Staff and Students Publications

Detection of organismal mosaic states for variant alleles faces technical and analytical challenges, as does the association of such variant alleles with susceptibility to neurologic disease. In this issue of Cell Genomics, Maury et al.¹ reanalyze genotyping arrays of a schizophrenia cohort providing evidence for the contribution of somatic structural variant mutagenesis and rare variant alleles.

A Biologic-Device Combination Product Delivering Tumor-Derived Antigens Elicits Immunogenic Cell Death-Associated Immune Responses Against Glioblastoma, Christopher Cultrara, Christopher Uhl, Kenneth Kirby, Essam Abed Elrazaq, Amelia Zellander, David W. Andrews, Charles B. Scott, Lorenzo Galluzzi, Mark A. Exley, Jenny Zilberberg

Department of Neurosurgery Faculty Papers

Background IGV-001 is a personalized, autologous cancer cell-based immunotherapy conceived to deliver a tumor-derived antigenic payload in the context of immunostimulatory signals to patients with glioblastoma (GBM). IGV-001 consists of patient-derived GBM cells treated with an antisense oligodeoxynucleotide against insulin-like growth factor 1 receptor (IGF1R) and placed in proprietary biodiffusion chambers (BDCs). The BDCs are then exposed to 5–6 Gy radiation and implanted at abdominal sites for ~48 hours. IGV-001 has previously been shown to be generally safe with promising clinical activity in newly diagnosed GBM patients.

Methods Mouse (m) or human (h) variants of IGV-001 …

Implementation And Assessment Of A Laparotomy-Assisted Three-Port Fetoscopic Spina Bifida Repair Program, Corinna Keil, Siegmund Köhler, Benjamin Sass, Maximilian Schulze, Gerald Kalmus, Michael Belfort, Nicolas Schmitt, Daniele Diehl, Alice King, Stefanie Groß, Caitlin D Sutton, Luc Joyeux, Mirjam Wege, Christopher Nimsky, Wiliam E Whitehead, Eberhard Uhl, Thierry A G M Huisman, Bernd A Neubauer, Stefanie Weber, Helmut Hummler, Roland Axt-Fliedner, Ivonne Bedei

Faculty, Staff and Students Publications

Open spina bifida (OSB) is a congenital, non-lethal malformation with multifactorial etiology. Fetal therapy can be offered under certain conditions to parents after accurate prenatal diagnostic and interdisciplinary counseling. Since the advent of prenatal OSB surgery, various modifications of the original surgical techniques have evolved, including laparotomy-assisted fetoscopic repair. After a two-year preparation time, the team at the University of Giessen and Marburg (UKGM) became the first center to provide a three-port, three-layer fetoscopic repair of OSB via a laparotomy-assisted approach in the German-speaking area. We point out that under the guidance of experienced centers and by intensive multidisciplinary preparation …

An Ontology-Based Approach For Harmonization And Cross-Cohort Query Of Alzheimer’S Disease Data Resources, Xubing Hao, Xiaojin Li, Guo-Qiang Zhang, Cui Tao, Paul E Schulz, Licong Cui

Faculty, Staff and Student Publications

BACKGROUND: In the United States, the National Alzheimer's Coordinating Center (NACC) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) are two major data sharing resources for Alzheimer's Disease (AD) research. NACC and ADNI strive to make their data more FAIR (findable, interoperable, accessible and reusable) for the broader research community. However, there is limited work harmonizing and supporting cross-cohort interoperability of the two resources.

METHOD: In this paper, we leverage an ontology-based approach to harmonize data elements in the two resources and develop a web-based query system to search patient cohorts across the two resources. We first mapped data elements across …

Piezo2 In Somatosensory Neurons Controls Gastrointestinal Transit, M Rocio Servin-Vences, Ruby M Lam, Alize Koolen, Yu Wang, Dimah N Saade, Meaghan Loud, Halil Kacmaz, Suzanne Frausto, Yunxiao Zhang, Arthur Beyder, Kara L Marshall, Carsten G Bönnemann, Alexander T Chesler, Ardem Patapoutian

Duncan NRI Faculty and Staff Publications

The gastrointestinal tract is in a state of constant motion. These movements are tightly regulated by the presence of food and help digestion by mechanically breaking down and propelling gut content. Mechanical sensing in the gut is thought to be essential for regulating motility; however, the identity of the neuronal populations, the molecules involved, and the functional consequences of this sensation are unknown. Here, we show that humans lacking PIEZO2 exhibit impaired bowel sensation and motility. Piezo2 in mouse dorsal root, but not nodose ganglia is required to sense gut content, and this activity slows down food transit rates in …

Monoallelic Variation In Dhx9, The Gene Encoding The Dexh-Box Helicase Dhx9, Underlies Neurodevelopment Disorders And Charcot-Marie-Tooth Disease, Daniel G Calame, Tianyu Guo, Chen Wang, Lillian Garrett, Angad Jolly, Moez Dawood, Alina Kurolap, Noa Zunz Henig, Jawid M Fatih, Isabella Herman, Haowei Du, Tadahiro Mitani, Lore Becker, Birgit Rathkolb, Raffaele Gerlini, Claudia Seisenberger, Susan Marschall, Jill V Hunter, Amanda Gerard, Alexis Heidlebaugh, Thomas Challman, Rebecca C Spillmann, Shalini N Jhangiani, Zeynep Coban-Akdemir, Seema Lalani, Lingxiao Liu, Anya Revah-Politi, Alejandro Iglesias, Edwin Guzman, Evan Baugh, Nathalie Boddaert, Sophie Rondeau, Clothide Ormieres, Giulia Barcia, Queenie K G Tan, Isabelle Thiffault, Tomi Pastinen, Kazim Sheikh, Suur Biliciler, Davide Mei, Federico Melani, Vandana Shashi, Yuval Yaron, Mary Steele, Emma Wakeling, Elsebet Østergaard, Lusine Nazaryan-Petersen, Undiagnosed Diseases Network, Francisca Millan, Teresa Santiago-Sim, Julien Thevenon, Ange-Line Bruel, Christel Thauvin-Robinet, Denny Popp, Konrad Platzer, Pawel Gawlinski, Wojciech Wiszniewski, Dana Marafi, Davut Pehlivan, Jennifer E Posey, Richard A Gibbs, Valerie Gailus-Durner, Renzo Guerrini, Helmut Fuchs, Martin Hrabě De Angelis, Sabine M Hölter, Hoi-Hung Cheung, Shen Gu, James R Lupski

Faculty, Staff and Student Publications

DExD/H-box RNA helicases (DDX/DHX) are encoded by a large paralogous gene family; in a subset of these human helicase genes, pathogenic variation causes neurodevelopmental disorder (NDD) traits and cancer. DHX9 encodes a BRCA1-interacting nuclear helicase regulating transcription, R-loops, and homologous recombination and exhibits the highest mutational constraint of all DDX/DHX paralogs but remains unassociated with disease traits in OMIM. Using exome sequencing and family-based rare-variant analyses, we identified 20 individuals with de novo, ultra-rare, heterozygous missense or loss-of-function (LoF) DHX9 variant alleles. Phenotypes ranged from NDDs to the distal symmetric polyneuropathy axonal Charcot-Marie-Tooth disease (CMT2). Quantitative Human Phenotype Ontology (HPO) …

Novel Murine Glioblastoma Models That Reflect The Immunotherapy Resistance Profile Of A Human Disease, Chao-Hsien Chen, Renee L Chin, Genevieve P Hartley, Spencer T Lea, Brian J Engel, Cheng-En Hsieh, Rishika Prasad, Jason Roszik, Takashi Shingu, Gregory A Lizee, Amy B Heimberger, Steven W Millward, Jian Hu, David S Hong, Michael A Curran

Faculty, Staff and Student Publications

BACKGROUND: The lack of murine glioblastoma models that mimic the immunobiology of human disease has impeded basic and translational immunology research. We, therefore, developed murine glioblastoma stem cell lines derived from Nestin-CreERT2QkL/L; Trp53L/L; PtenL/L (QPP) mice driven by clinically relevant genetic mutations common in human glioblastoma. This study aims to determine the immune sensitivities of these QPP lines in immunocompetent hosts and their underlying mechanisms.

METHODS: The differential responsiveness of QPP lines was assessed in the brain and flank in untreated, anti-PD-1, or anti-CTLA-4 treated mice. The impact of genomic landscape on the responsiveness of each tumor was measured through …

Ot's Role In Facilitating Successful Role Transition For Informal Caregivers Of People Living With Dementia, Kiyatta Freeman, Monica Watford, Evyline Chioma

Summer 2023 Virtual OTD Capstone Symposium

The aim of this capstone project was to identify education and training needs for family caregivers of individuals living with dementia and create an educational workshop based on these identified needs. This workshop is a dementia training course focused on education on the dementia diagnosis and effective care strategies to promote occupational participation and safety for the care recipient and the caregiver. The aim is to improve care competency, reduce stress, and facilitate role transition.

The Importance Of Addressing Sleep As An Occupation Within Assisted Living Communities, Brittany Kiattitananan, Kendra Orcutt, Lisa Griggs-Stapleton

Summer 2023 Virtual OTD Capstone Symposium

Around 40-70% of older adults have difficulty sleeping (Sheth & Thomas, 2019). This poster presents an occupation-based sleep intervention program developed for residents of an assisted living community and serves to inform OT practitioners on addressing sleep in their own practice.

Persistence To Anti-Cgrp Monoclonal Antibodies And Onabotulinumtoxina Among Patients With Migraine: A Retrospective Cohort Study, Larry Charleston, Brian Talon, Christine Sullivan, Carlton Anderson, Steven Kymes, Stephane A. Regnier, Seema Soni-Brahmbhatt, Stephanie J. Nahas

Department of Jefferson Headache Center Papers and Presentations

BACKGROUND: To date, real-world evidence on persistence to anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAbs) or onabotulinumtoxinA have excluded eptinezumab. This retrospective cohort study was performed to compare treatment persistency among patients with migraine on anti-CGRP mAbs (erenumab, fremanezumab, galcanezumab, or eptinezumab) or onabotulinumtoxinA.

METHODS: This retrospective study used IQVIA PharmMetrics data. Adult patients with migraine treated with an anti-CGRP mAb or onabotulinumtoxinA who had 12 months of continuous insurance enrollment before starting treatment were included. A "most recent treatment episode" analysis was used in which the most recent episode was defined as the latest treatment period with the same …

Implementation Of Tai Chi Among Individuals With Dementia In Long-Term Memory Care, Patricia I. Cordova, Lisa Griggs-Stapleton, Kim Broussard

Summer 2023 Virtual OTD Capstone Symposium

This project focused on a dementia population within long-term care, where increased disablement occurs. A Tai Chi program was implemented into the daily routine of individuals in a long-term memory care facility to improve dynamic sitting balance for the performance of daily occupations.

The Sandwich Generation Of Aging Parents With Dementia: An Occupation-Based Caregiver Program, Gabrielle Amaya, Lisa Griggs-Stapleton, Kylee Hall

Summer 2023 Virtual OTD Capstone Symposium

Despite the high prevalence of caregiver burnout, caregivers’ needs are unrecognized because the focus is on caregiver quality of life, experience, or service utilization (Frankenstein & Jahn, 2020). This program aims to identify ways to provide specific support to promote caregiver ADL participation through the use of a web-based training and education program.

Chronic Nsmase Inhibition Suppresses Neuronal Exosome Spreading And Sex-Specifically Attenuates Amyloid Pathology In App Knock-In Alzheimer's Disease Mice, Francesca E. Mowry, Francisco Espejo-Porras, Shijie Jin, Zainuddin Quadri, Limin Wu, Marcela Bertolio, Rachel Jarvis, Caroline Reynolds, Rashed Alananzeh, Erhard Bieberich, Yongjie Yang

Markey Cancer Center Faculty Publications

Female biased pathology and cognitive decline in Alzheimer’s disease (AD) have been consistently observed with unclear underlying mechanisms. Although brain sphingolipid ceramide is elevated in AD patients, whether and how ceramide may contribute to sex-specific differences in amyloid pathology is unknown. Here we investigated the sex-specific impact of chronic pharmacological inhibition of neutral sphingomyelinase (nSMase), a key enzyme responsible for ceramide metabolism, on in vivo neuron-derived exosome dynamics, Aβ plaque load, and cognitive function in the APPNL-F/NL-F knock-in (APP NL-F) AD mouse model. Our results found sex-specific increase of cortical C20:0 ceramide and brain exosome levels only in APP NL-F …

Inhibition Of Acid Sphingomyelinase Reduces Reactive Astrocyte Secretion Of Mitotoxic Extracellular Vesicles And Improves Alzheimer’S Disease Pathology In The 5xfad Mouse, Simone M. Crivelli, Zainuddin Quadri, Hemendra J. Vekaria, Zhihui Zhu, Priyanka Tripathi, Ahmed Elsherbini, Liping Zhang, Patrick G. Sullivan, Erhard Bieberich

Markey Cancer Center Faculty Publications

In Alzheimer’s disease (AD), reactive astrocytes produce extracellular vesicles (EVs) that affect mitochondria in neurons. Here, we show that Aβ-induced generation of the sphingolipid ceramide by acid sphingomyelinase (A-SMase) triggered proinflammatory cytokine (C1q, TNF-α, IL-1α) release by microglia, which induced the reactive astrocytes phenotype and secretion of EVs enriched with ceramide. These EVs impeded the capacity of neurons to respond to energy demand. Inhibition of A-SMase with Arc39 and Imipramine reduced the secretion of cytokines from microglia, prompting us to test the effect of Imipramine on EV secretion and AD pathology in the 5xFAD mouse model. Brain derived-EVs from 5xFAD …

Isolated Cervical Dystonia: Diagnosis And Classification, Alberto Albanese, Kailash P Bhatia, Francisco Cardoso, Cynthia Comella, Giovanni Defazio, Victor S C Fung, Mark Hallett, Joseph Jankovic, Hyder A Jinnah, Ryuji Kaji, Joachim K Krauss, Anthony Lang, Eng King Tan, Marina A J Tijssen, Marie Vidailhet

Faculty, Staff and Students Publications

This document presents a consensus on the diagnosis and classification of isolated cervical dystonia (iCD) with a review of proposed terminology. The International Parkinson and Movement Disorder Society Dystonia Study Group convened a panel of experts to review the main clinical and diagnostic issues related to iCD and to arrive at a consensus on diagnostic criteria and classification. These criteria are intended for use in clinical research, but also may be used to guide clinical practice. The benchmark is expert clinical observation and evaluation. The criteria aim to systematize the use of terminology as well as the diagnostic process, to …

Use Of Video Alone For Differentiation Of Epileptic Seizures From Non-Epileptic Spells: A Systematic Review And Meta-Analysis, Cemal Karakas, Liam D Ferreira, Zulfi Haneef

Faculty, Staff and Students Publications

Introduction: Review of videos (without electroencephalography) to differentiate epileptic seizures (ES) from non-epileptic spells (NES) may be helpful where epilepsy monitoring is not feasible. Previous studies of video-based diagnosis have suffered from variable accuracy, sensitivity, and specificity.

Methods: We systematically reviewed relevant literature in PubMed, Embase, and Web of Science from inception to September 2022, identifying articles that reported on the video-based diagnosis of ES and NES. In primary analysis, for each study, the most expert group was chosen when different groups of reviewers classified the videos (e.g., epilepsy specialists and general neurologists). In secondary analysis, we compared the diagnostic …

Exploring Gastrointestinal Health In Mecp2 Duplication Syndrome, Davut Pehlivan, Muharrem Ak, Daniel G Glaze, Bernhard Suter, Kathleen J Motil

Faculty, Staff and Students Publications

BACKGROUND: MECP2 duplication syndrome (MDS) is a rare neurogenetic syndrome caused by duplications of MECP2 at the Xq28 region. Although constipation and gastrointestinal reflux are reported in MDS, a comprehensive characterization of gastrointestinal health has not been fully explored.

METHODS: We conducted a parent survey to explore the characteristics of gastrointestinal health in individuals with MDS using a secure online registry and compared differences in gastrointestinal symptoms between individuals with MDS and those with Rett syndrome (RTT).

KEY RESULTS: One hundred six surveys were analyzed. Symptoms commonly associated with constipation occurred in 72% to 89% of MDS individuals. Eleven percent …