Neurology Commons^™

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 …

Variants In Zfx Are Associated With An X-Linked Neurodevelopmental Disorder With Recurrent Facial Gestalt\, James L Shepherdson, Katie Hutchison, Dilan Wellalage Don, George Mcgillivray, Tae-Ik Choi, Carolyn A Allan, David J Amor, Siddharth Banka, Donald G Basel, Laura D Buch, Deanna Alexis Carere, Renée Carroll, Jill Clayton-Smith, Ali Crawford, Morten Dunø, Laurence Faivre, Christopher P Gilfillan, Nina B Gold, Karen W Gripp, Emma Hobson, Alexander M Holtz, A Micheil Innes, Bertrand Isidor, Adam Jackson, Panagiotis Katsonis, Leila Amel Riazat Kesh, Genomics England Research Consortium;, Sébastien Küry, François Lecoquierre, Paul Lockhart, Julien Maraval, Naomichi Matsumoto, Julie Mccarrier, Josephine Mccarthy, Noriko Miyake, Lip Hen Moey, Andrea H Németh, Elsebet Østergaard, Rushina Patel, Kate Pope, Jennifer E Posey, Rhonda E Schnur, Marie Shaw, Elliot Stolerman, Julie P Taylor, Erin Wadman, Emma Wakeling, Susan M White, Lawrence C Wong, James R Lupski, Olivier Lichtarge, Mark A Corbett, Jozef Gecz, Charles M Nicolet, Peggy J Farnham, Cheol-Hee Kim, Marwan Shinawi

Duncan NRI Faculty and Staff Publications

Pathogenic variants in multiple genes on the X chromosome have been implicated in syndromic and non-syndromic intellectual disability disorders. ZFX on Xp22.11 encodes a transcription factor that has been linked to diverse processes including oncogenesis and development, but germline variants have not been characterized in association with disease. Here, we present clinical and molecular characterization of 18 individuals with germline ZFX variants. Exome or genome sequencing revealed 11 variants in 18 subjects (14 males and 4 females) from 16 unrelated families. Four missense variants were identified in 11 subjects, with seven truncation variants in the remaining individuals. Clinical findings included …

Endovascular Thrombectomy For Large Ischemic Stroke Across Ischemic Injury And Penumbra Profiles., Amrou Sarraj, Ameer E Hassan, Michael G Abraham, Santiago Ortega-Gutierrez, Scott E Kasner, Muhammad Shazam Hussain, Michael Chen, Leonid Churilov, Hannah Johns, Clark W Sitton, Vignan Yogendrakumar, Felix C Ng, Deep K Pujara, Spiros Blackburn, Sophia Sundararajan, Yin C Hu, Nabeel A Herial, Juan F Arenillas, Jenny P Tsai, Ronald F Budzik, William J Hicks, Osman Kozak, Bernard Yan, Dennis J Cordato, Nathan W Manning, Mark W Parsons, Andrew Cheung, Ricardo A Hanel, Amin N Aghaebrahim, Teddy Y Wu, Pere Cardona Portela, Chirag D Gandhi, Fawaz Al-Mufti, Natalia Pérez De La Ossa, Joanna D Schaafsma, Jordi Blasco, Navdeep Sangha, Steven Warach, Timothy J Kleinig, Faris Shaker, Faisal Al Shaibi, Gabor Toth, Mohammad A Abdulrazzak, Gagan Sharma, Abhishek Ray, Jeffrey Sunshine, Amanda Opaskar, Kelsey R Duncan, Wei Xiong, Edgar A Samaniego, Laith Maali, Colleen G Lechtenberg, Arturo Renú, Nirav Vora, Thanh Nguyen, Johanna T Fifi, Stavropoula I Tjoumakaris, Pascal Jabbour, Georgios Tsivgoulis, Vitor Mendes Pereira, Maarten G Lansberg, Michael Degeorgia, Cathy A Sila, Nicholas Bambakidis, Michael D Hill, Stephen M Davis, Lawrence Wechsler, James C Grotta, Marc Ribo, Greg W Albers, Bruce C Campbell

Neuroscience Articles

IMPORTANCE: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain.

OBJECTIVE: To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect.

DESIGN, SETTING, AND PARTICIPANTS: An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 …

Postconcussive Symptoms After Early Childhood Concussion, Dominique Dupont, Ken Tang, Cindy Beaudoin, Fanny Dégeilh, Isabelle Gagnon, Keith Owen Yeates, Sean C Rose, Jocelyn Gravel, Brett Burstein, Antonia S Stang, Rachel M Stanley, Roger L Zemek, Miriam H Beauchamp, Perc Koala Study

Faculty, Staff and Student Publications

IMPORTANCE: Research on postconcussive symptoms (PCS) following early childhood concussion has been hindered by a lack of measures suitable for this age group, resulting in a limited understanding of their evolution in young children.

OBJECTIVE: To document PCS in the first 3 months after early childhood concussion using a developmentally appropriate measure.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data collected at 3 Canadian and 1 US urban pediatric emergency departments (EDs) and 8 Canadian daycares from December 2018 to December 2022 as part of the Kids' Outcomes and Long-Term Abilities (KOALA) project, a prospective, multicenter, longitudinal cohort study. …

Neuroinvasive West Nile Virus Infection In Immunosuppressed And Immunocompetent Adults., Amir A Mbonde, David Gritsch, Ehab Y Harahsheh, Sabirah N Kasule, Shemonti Hasan, Angela M Parsons, Nan Zhang, Richard Butterfield, Harn Shiue, Kathryn A Norville, Jenna L Reynolds, Holenarasipur R Vikram, Brian Chong, Marie F Grill

Neuroscience Articles

IMPORTANCE: West Nile virus (WNV) is the leading cause of human arboviral disease in the US, peaking during summer. The incidence of WNV, including its neuroinvasive form (NWNV), is increasing, largely due to the expanding distribution of its vector, the Culex mosquito, and climatic changes causing heavy monsoon rains. However, the distinct characteristics and outcomes of NWNV in individuals who are immunosuppressed (IS) and individuals who are not IS remain underexplored.

OBJECTIVE: To describe and compare clinical and radiographic features, treatment responses, and outcomes of NWNV infection in individuals who are IS and those who are not IS.

DESIGN, SETTING, …

Risk Of Alzheimer's Disease And Related Dementias In Persons With Glaucoma: A National Cohort Study, Casey Crump, Jan Sundquist, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

PURPOSE: Glaucoma is a heterogeneous group of optic neuropathies that potentially may be associated with other cerebral neurodegenerative processes leading to dementia. However, prior studies have been inconsistent. We examined dementia risks after glaucoma diagnosis in a large population-based cohort.

DESIGN: National matched cohort study.

PARTICIPANTS: A total of 324 730 persons diagnosed with glaucoma during 1995-2017 in Sweden and 3 247 300 age- and sex-matched population-based controls without prior dementia.

METHODS: Cox regression was used to compute hazard ratios (HRs) for Alzheimer's disease (AD), vascular dementia (VaD), and all-cause dementia in persons with glaucoma compared with controls, adjusting for …

Heterozygous Map3k20 Variants Cause Ectodermal Dysplasia, Craniosynostosis, Sensorineural Hearing Loss, And Limb Anomalies, Daniel Brooks, Elizabeth Burke, Sukyeong Lee, Tanya N Eble, Melanie O'Leary, Ikeoluwa Osei-Owusu, Heidi L Rehm, Shweta U Dhar, Lisa Emrick, David Bick, Michelle Nehrebecky, Ellen Macnamara, Dídac Casas-Alba, Judith Armstrong, Carolina Prat, Antonio F Martínez-Monseny, Francesc Palau, Pengfei Liu, David Adams, Undiagnosed Diseases Network, Seema Lalani, Jill A Rosenfeld, Lindsay C Burrage

Faculty, Staff and Students Publications

Biallelic pathogenic variants in MAP3K20, which encodes a mitogen-activated protein kinase, are a rare cause of split-hand foot malformation (SHFM), hearing loss, and nail abnormalities or congenital myopathy. However, heterozygous variants in this gene have not been definitively associated with a phenotype. Here, we describe the phenotypic spectrum associated with heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20. We report five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in this specific region of the gene. …

Association Of Plasma Ykl-40 With Mri, Csf, And Cognitive Markers Of Brain Health And Dementia, Matthew P Pase, Jayandra J Himali, Raquel Puerta, Alexa S Beiser, Mitzi M Gonzales, Claudia L Satizabal, Qiong Yang, Hugo J Aparicio, Daniel J Kojis, Charles S Decarli, Oscar L Lopez, Will Longstreth, Vilmundur Gudnason, Thomas H Mosley, Joshua C Bis, Alison Fohner, Bruce M Psaty, Mercè Boada, Pablo García-González, Sergi Valero, Marta Marquié, Russell Tracy, Lenore J Launer, Agustín Ruiz, Myriam Fornage, Sudha Seshadri

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Higher YKL-40 levels in the CSF are a known biomarker of brain inflammation. We explored the utility of plasma YKL-40 as a biomarker for accelerated brain aging and dementia risk.

METHODS: We performed cross-sectional and prospective analyses of 4 community-based cohorts in the United States or Europe: the Age, Gene/Environment Susceptibility-Reykjavik Study, Atherosclerosis Risk in the Communities study, Coronary Artery Risk Development in Young Adults study, and Framingham Heart Study (FHS). YKL-40 was measured from stored plasma by a single laboratory using Mesoscale Discovery with levels log transformed and standardized within each cohort. Outcomes included MRI total …

Impact Of An Integrated Health, Nutrition, And Early Child Stimulation And Responsive Care Intervention Package Delivered To Preterm Or Term Small For Gestational Age Babies During Infancy On Growth And Neurodevelopment: Study Protocol Of An Individually Randomized Controlled Trial In India (Small Babies Trial), Ranadip Chowdhury, Rukman Manapurath, Ingvild Fossgard Sandøy, Ravi Prakash Upadhyay, Neeta Dhabhai, Saijuddin Shaikh, Harish Chellani, Tarun Shankar Choudhary, Abhinav Jain, Jose Martines, Nita Bhandari, Tor A Strand, Sunita Taneja

Faculty, Staff and Student Publications

BACKGROUND: Preterm and term small for gestational age (SGA) babies are at high risk of experiencing malnutrition and impaired neurodevelopment. Standalone interventions have modest and sometimes inconsistent effects on growth and neurodevelopment in these babies. For greater impact, intervention may be needed in multiple domains-health, nutrition, and psychosocial care and support. Therefore, the combined effects of an integrated intervention package for preterm and term SGA on growth and neurodevelopment are worth investigating.

METHODS: An individually randomized controlled trial is being conducted in urban and peri-urban low to middle-socioeconomic neighborhoods in South Delhi, India. Infants are randomized (1:1) into two strata …

Discovery And Clinical Proof-Of-Concept Of Rly-2608, A First-In-Class Mutant-Selective Allosteric Pi3kα Inhibitor That Decouples Antitumor Activity From Hyperinsulinemia, Andreas Varkaris, Ermira Pazolli, Hakan Gunaydin, Qi Wang, Levi Pierce, Alessandro A Boezio, Artemisa Bulku, Lucian Dipietro, Cary Fridrich, Adam Frost, Fabrizio Giordanetto, Erika P Hamilton, Katherine Harris, Michael Holliday, Tamieka L Hunter, Amanda Iskandar, Yongli Ji, Alexandre Larivée, Jonathan R Larochelle, André Lescarbeau, Fabien Llambi, Brenda Lormil, Mary M Mader, Brenton G Mar, Iain Martin, Thomas H Mclean, Klaus Michelsen, Yakov Pechersky, Erika Puente-Poushnejad, Kevin Raynor, Dipali Rogala, Ramin Samadani, Alison M Schram, Kelley Shortsleeves, Sweta Swaminathan, Shahein Tajmir, Gege Tan, Yong Tang, Roberto Valverde, Bryan Wehrenberg, Jeremy Wilbur, Bret R Williams, Hongtao Zeng, Hanmo Zhang, W Patrick Walters, Beni B Wolf, David E Shaw, Donald A Bergstrom, James Watters, James S Fraser, Pascal D Fortin, D Randal Kipp

Faculty, Staff and Student Publications

PIK3CA (PI3Kα) is a lipid kinase commonly mutated in cancer, including ∼40% of hormone receptor–positive breast cancer. The most frequently observed mutants occur in the kinase and helical domains. Orthosteric PI3Kα inhibitors suffer from poor selectivity leading to undesirable side effects, most prominently hyperglycemia due to inhibition of wild-type (WT) PI3Kα. Here, we used molecular dynamics simulations and cryo-electron microscopy to identify an allosteric network that provides an explanation for how mutations favor PI3Kα activation. A DNA-encoded library screen leveraging electron microscopy-optimized constructs, differential enrichment, and an orthosteric-blocking compound led to the identification of RLY-2608, a first-in-class allosteric mutant-selective inhibitor …

Thrombectomy With The Preset Vs Solitaire Stent Retrievers As First-Line Large Vessel Occlusion Stroke Treatment: A Randomized Clinical Trial., Raul G Nogueira, Donald Lobsien, Joachim Klisch, Daniel Pielenz, Elmar Lobsien, Eric Sauvageau, Nima Aghaebrahim, Markus Möhlenbruch, Dominik Vollherbst, Christian Ulfert, Hormozd Bozorgchami, Wayne Clark, Ryan Priest, Edgar A Samaniego, Santiago Ortega-Gutierrez, Malik Ghannam, Demetrius Lopes, Joshua Billingsley, Kiffon Keigher, Diogo C Haussen, Alhamza R Al-Bayati, Adnan Siddiqui, Elad Levy, Michael Chen, Stephan Munich, Peter Schramm, Tobias Boppel, Sandra Narayanan, Bradley A Gross, Christian Roth, Tobias Boeckh-Behrens, Ameer Hassan, Johanna Fifi, Ron F Budzik, Jason Tarpley, Robert M Starke, Eytan Raz, Gary Brogan, David S Liebeskind, Ricardo A Hanel

Neuroscience Articles

IMPORTANCE: Stent retriever-based thrombectomy is highly beneficial in large vessel occlusion (LVO) strokes. Many stent retriever designs are currently available, but comparison of these technologies in well-conducted studies is lacking.

OBJECTIVE: To determine whether thrombectomy for LVO stroke with the pRESET stent retriever is noninferior to treatment with the Solitaire stent retriever.

DESIGN, SETTING, AND PARTICIPANTS: This study was a multicenter, prospective, randomized, controlled, open-label, adaptive, noninferiority trial with blinded primary end point evaluation. Between October 2019 and February 2022, multicenter participation occurred across 19 research hospitals and/or universities in the US and 5 in Germany. Patients with LVO stroke …

Trigeminal Neuralgia As A Primary Demyelinating Disease: Potential Multimodal Evidence And Remaining Controversies, Seyed H Mousavi, John W Lindsey, Karin N Westlund, Sascha R A Alles

Faculty, Staff and Student Publications

Trigeminal neuralgia is a heterogeneous disorder with likely multifactorial and complex etiology; however, trigeminal nerve demyelination and injury are observed in almost all patients with trigeminal neuralgia. The current management strategies for trigeminal neuralgia primarily involve anticonvulsants and surgical interventions, neither of which directly address demyelination, the pathological hallmark of trigeminal neuralgia, and treatments targeting demyelination are not available. Demyelination of the trigeminal nerve has been historically considered a secondary effect of vascular compression, and as a result, trigeminal neuralgia is not recognized nor treated as a primary demyelinating disorder. In this article, we review the evolution of our understanding …

Isolated Abducens Nerve Palsy: A Rare Manifestation Of Recurrent Extramedullary Myeloma, Neal Joshi, Joy Li, Ajit Karambelkar, Payton Boere

Jefferson Hospital Staff Papers and Presentations

Multiple myeloma is a plasma cell neoplasm, which may present as a solitary plasmacytoma and, uncommonly, as an extramedullary plasmacytoma. Intracranial plasmacytomas may manifest in central nervous system involvement as cranial nerve palsies. Cranial nerve six palsy is the most common in cases of malignancy. However, isolated abducens palsy presenting as multiple myeloma recurrence is very uncommon. Here, we detail two cases in which intracranial plasmacytoma lesions were present within the region of the Dorello canal, resulting in acute isolated unilateral diplopia from disease recurrence in the absence of systemic marrow involvement.

Evaluating Noninvasive Brain Stimulation To Treat Overactive Bladder In Individuals With Multiple Sclerosis: A Randomized Controlled Trial Protocol, Betsy H Salazar, Kristopher A Hoffman, John A Lincoln, Christof Karmonik, Hamida Rajab, Santosh A Helekar, Rose Khavari

Faculty, Staff and Student Publications

Background

Multiple Sclerosis (MS) is an often debilitating disease affecting the myelin sheath that encompasses neurons. It can be accompanied by a myriad of pathologies and adverse effects such as neurogenic lower urinary tract dysfunction (NLUTD). Current treatment modalities for resolving NLUTD focus mainly on alleviating symptoms while the source of the discomfort emanates from a disruption in brain to bladder neural circuitry. Here, we leverage functional magnetic resonance imaging (fMRI), repetitive transcranial magnetic stimulation (rTMS) protocols and the brains innate neural plasticity to aid in resolving overactive bladder (OAB) symptoms associated with NLUTD.

Methods

By employing an advanced neuro-navigation …

Comparing Cognitive Tests And Smartphone-Based Assessment In 2 Us Community-Based Cohorts., Ileana De Anda-Duran, Preeti Sunderaraman, Edward Searls, Shirine Moukaled, Xuanyi Jin, Zachary Popp, Cody Karjadi, Phillip H Hwang, Huitong Ding, Sherral Devine, Ludy C Shih, Spencer Low, Honghuang Lin, Vijaya B Kolachalama, Lydia Bazzano, David J Libon, Rhoda Au

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Smartphone-based cognitive assessments have emerged as promising tools, bridging gaps in accessibility and reducing bias in Alzheimer disease and related dementia research. However, their congruence with traditional neuropsychological tests and usefulness in diverse cohorts remain underexplored.

METHODS AND RESULTS: A total of 406 FHS (Framingham Heart Study) and 59 BHS (Bogalusa Heart Study) participants with traditional neuropsychological tests and digital assessments using the Defense Automated Neurocognitive Assessment (DANA) smartphone protocol were included. Regression models investigated associations between DANA task digital measures and a neuropsychological global cognitive

CONCLUSIONS: Our findings demonstrate that smartphone-based cognitive assessments exhibit concurrent validity with a …

Comparative Transcriptomic Analysis Of Cerebellar Astrocytes Across Developmental Stages And Brain Regions, Wookbong Kwon, Dong-Joo Choi, Kwanha Yu, Michael R Williamson, Sanjana Murali, Yeunjung Ko, Junsung Woo, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes are the most abundant glial cell type in the central nervous system, and they play a crucial role in normal brain function. While gliogenesis and glial differentiation occur during perinatal cerebellar development, the processes that occur during early postnatal development remain obscure. In this study, we conducted transcriptomic profiling of postnatal cerebellar astrocytes at postnatal days 1, 7, 14, and 28 (P1, P7, P14, and P28), identifying temporal-specific gene signatures at each specific time point. Comparing these profiles with region-specific astrocyte differentially expressed genes (DEGs) published for the cortex, hippocampus, and olfactory bulb revealed cerebellar-specific gene signature across these …

Pediatric Medical Subspecialist Use In Outpatient Settings, Christopher B Forrest, Candice P Chen, Eliana M Perrin, Christopher J Stille, Ruth Cooper, Katherine Harris, Qian Luo, Mitchell G Maltenfort, Lauren E Parlett

Faculty, Staff and Student Publications

Importance

A first step toward understanding whether pediatric medical subspecialists are meeting the needs of the nation’s children is describing rates of use and trends over time.

Objectives

To quantify rates of outpatient pediatric medical subspecialty use.

Design, Setting, and Participants

This repeated cross-sectional study of annual subspecialist use examined 3 complementary data sources: electronic health records from PEDSnet (8 large academic medical centers [January 1, 2010, to December 31, 2021]); administrative data from the Healthcare Integrated Research Database (HIRD) (14 commercial health plans [January 1, 2011, to December 31, 2021]); and administrative data from the Transformed Medicaid Statistical Information …

Digital Clock Drawing As An Alzheimer's Disease Susceptibility Biomarker: Associations With Genetic Risk Score And Apoe In Older Adults, L I Thompson, M Cummings, S Emrani, David J. Libon, A Ang, C Karjadi, R Au, C Liu

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia in older adults, but most people are not diagnosed until significant neuronal loss has likely occurred along with a decline in cognition. Non-invasive and cost-effective digital biomarkers for AD have the potential to improve early detection.

OBJECTIVE: We examined the validity of DCTclockTM (a digitized clock drawing task) as an AD susceptibility biomarker.

DESIGN: We used two primary independent variables, Apolipoprotein E (APOE) ε4 allele carrier status and polygenic risk score (PRS). We examined APOE and PRS associations with DCTclockTM composite scores as dependent measures.

SETTING: We used existing data …

An Objective Assessment Of Neuromotor Control Using A Smartphone App After Repeated Subconcussive Blast Exposure, Charlend K. Howard, Masahiro Yamada, Marcia Dovel, Rie Leverett, Alexander Hill, Kenneth A. Manlapaz, David O. Keyser, Rene S. Hernandez, Sheilah S. Rowe, Walter S. Carr, Michael S. Roy, Christopher K. Rhea

Rehabilitation Sciences Faculty Publications

Subconcussive blast exposure has been shown to alter neurological functioning. However, the extent to which neurological dysfunction persists after blast exposure is unknown. This longitudinal study examined the potential short- and long-term effects of repeated subconcussive blast exposure on neuromotor performance from heavy weapons training in military personnel. A total of 214 participants were assessed; 137 were exposed to repeated subconcussive blasts and 77 were not exposed to blasts (controls). Participants completed a short stepping-in-place task while an Android smartphone app placed on their thigh recorded movement kinematics. We showed acute suppression of neuromotor variability 6 h after subconcussive blast …

Responsive Neurostimulation For People With Drug-Resistant Epilepsy And Autism Spectrum Disorder, Madeline C Fields, Christina Marsh, Onome Eka, Emily A Johnson, Lara V Marcuse, Churl-Su Kwon, James J Young, Maite Lavega-Talbott, Mohankumar Kurukumbi, Gretchen Von Allmen, John Zempel, Daniel Friedman, Nathalie Jette, Anuradha Singh, Ji Yeoun Yoo, Leah Blank, Fedor Panov, Saadi Ghatan

Faculty, Staff and Student Publications

PURPOSE: Individuals with autism spectrum disorder (ASD) have comorbid epilepsy at much higher rates than the general population, and about 30% will be refractory to medication. Patients with drug-resistant epilepsy (DRE) should be referred for surgical evaluation, yet many with ASD and DRE are not resective surgical candidates. The aim of this study was to examine the response of this population to the responsive neurostimulator (RNS) System.

METHODS: This multicenter study evaluated patients with ASD and DRE who underwent RNS System placement. Patients were included if they had the RNS System placed for 1 year or more. Seizure reduction and …

Thalamic Atrophy And Dysconnectivity Are Associated With Cognitive Impairment In A Multi-Center, Clinical Routine, Real-Word Study Of People With Relapsing-Remitting Multiple Sclerosis., Robert Zivadinov, Niels Bergsland, Dejan Jakimovski, Bianca Weinstock-Guttman, Lorena Lorefice, Menno M Schoonheim, Sarah A Morrow, Mary Ann Picone, Gabriel Pardo, Myassar Zarif, Mark Gudesblatt, Jacqueline A Nicholas, Andrew Smith, Samuel Hunter, Stephen Newman, Mahmoud A Abdelrazek, Ina Hoti, Jon Riolo, Diego Silva, Tom A Fuchs, Michael G Dwyer, Ralph Hb Benedict

Neuroscience Articles

BACKGROUND: Prior research has established a link between thalamic pathology and cognitive impairment (CI) in people with multiple sclerosis (pwMS). However, the translation of these findings to pwMS in everyday clinical settings has been insufficient.

OBJECTIVE: To assess which global and/or thalamic imaging biomarkers can be used to identify pwMS at risk for CI and cognitive worsening (CW) in a real-world setting.

METHODS: This was an international, multi-center (11 centers), longitudinal, retrospective, real-word study of people with relapsing-remitting MS (pwRRMS). Brain MRI exams acquired at baseline and follow-up were collected. Cognitive status was evaluated using the Symbol Digit Modalities Test …

Researching Covid To Enhance Recovery (Recover) Pediatric Study Protocol: Rationale, Objectives And Design, Rachel S Gross, Tanayott Thaweethai, Erika B Rosenzweig, James Chan, Lori B Chibnik, Mine S Cicek, Amy J Elliott, Valerie J Flaherman, Andrea S Foulkes, Margot Gage Witvliet, Richard Gallagher, Maria Laura Gennaro, Terry L Jernigan, Elizabeth W Karlson, Stuart D Katz, Patricia A Kinser, Lawrence C Kleinman, Michelle F Lamendola-Essel, Joshua D Milner, Sindhu Mohandas, Praveen C Mudumbi, Jane W Newburger, Kyung E Rhee, Amy L Salisbury, Jessica N Snowden, Cheryl R Stein, Melissa S Stockwell, Kelan G Tantisira, Moriah E Thomason, Dongngan T Truong, David Warburton, John C Wood, Shifa Ahmed, Almary Akerlundh, Akram N Alshawabkeh, Brett R Anderson, Judy L Aschner, Andrew M Atz, Robin L Aupperle, Fiona C Baker, Venkataraman Balaraman, Dithi Banerjee, Deanna M Barch, Arielle Baskin-Sommers, Sultana Bhuiyan, Marie-Abele C Bind, Amanda L Bogie, Tamara Bradford, Natalie C Buchbinder, Elliott Bueler, Hülya Bükülmez, B J Casey, Linda Chang, Maryanne Chrisant, Duncan B Clark, Rebecca G Clifton, Katharine N Clouser, Lesley Cottrell, Kelly Cowan, Viren D'Sa, Mirella Dapretto, Soham Dasgupta, Walter Dehority, Audrey Dionne, Kirsten B Dummer, Matthew D Elias, Shari Esquenazi-Karonika, Danielle N Evans, E Vincent S Faustino, Alexander G Fiks, Daniel Forsha, John J Foxe, Naomi P Friedman, Greta Fry, Sunanda Gaur, Dylan G Gee, Kevin M Gray, Stephanie Handler, Ashraf S Harahsheh, Keren Hasbani, Andrew C Heath, Camden Hebson, Mary M Heitzeg, Christina M Hester, Sophia Hill, Laura Hobart-Porter, Travis K F Hong, Carol R Horowitz, Daniel S Hsia, Matthew Huentelman, Kathy D Hummel, Katherine Irby, Joanna Jacobus, Vanessa L Jacoby, Pei-Ni Jone, David C Kaelber, Tyler J Kasmarcak, Matthew J Kluko, Jessica S Kosut, Angela R Laird, Jeremy Landeo-Gutierrez, Sean M Lang, Christine L Larson, Peter Paul C Lim, Krista M Lisdahl, Brian W Mccrindle, Russell J Mcculloh, Kimberly Mchugh, Alan L Mendelsohn, Torri D Metz, Julie Miller, Elizabeth C Mitchell, Lerraughn M Morgan, Eva M Müller-Oehring, Erica R Nahin, Michael C Neale, Manette Ness-Cochinwala, Sheila M Nolan, Carlos R Oliveira, Onyekachukwu Osakwe, Matthew E Oster, R Mark Payne, Michael A Portman, Hengameh Raissy, Isabelle G Randall, Suchitra Rao, Harrison T Reeder, Johana M Rosas, Mark W Russell, Arash A Sabati, Yamuna Sanil, Alice I Sato, Michael S Schechter, Rangaraj Selvarangan, S Kristen Sexson Tejtel, Divya Shakti, Kavita Sharma, Lindsay M Squeglia, Shubika Srivastava, Michelle D Stevenson, Jacqueline Szmuszkovicz, Maria M Talavera-Barber, Ronald J Teufel, Deepika Thacker, Felicia Trachtenberg, Mmekom M Udosen, Megan R Warner, Sara E Watson, Alan Werzberger, Jordan C Weyer, Marion J Wood, H Shonna Yin, William T Zempsky, Emily Zimmerman, Benard P Dreyer, Recover-Pediatric Consortium

Faculty, Staff and Students Publications

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.

OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of …

Parkinson's Disease And Other Alzheimer's Disease And Related Dementia Pathologies And The Progression Of Parkinsonism In Older Adults, Aron S Buchman, Lei Yu, Shahram Oveisgharan, Andrea R Zammit, Tianhao Wang, Joshua M Shulman, Veronique Vanderhorst, Sukrit Nag, David A Bennett

Faculty, Staff and Students Publications

BACKGROUND: The interrelationship of parkinsonism, Parkinson's disease (PD) and other Alzheimer's disease (AD) and Alzheimer's disease and related dementias (ADRD) pathologies is unclear.

OBJECTIVE: We examined the progression of parkinsonian signs in adults with and without parkinsonism, and their underlying brain pathologies.

METHODS: Annual parkinsonian signs were based on a modified Unified Parkinson's Disease Rating Scale. We used linear mixed effects models to compare the progression of parkinsonian signs in 3 groups categorized based on all available clinical evaluations: Group1 (never parkinsonism or clinical PD), Group2 (ever parkinsonism, but never clinical PD), Group3 (ever clinical PD). In decedents, we examined …

Validation Of A New Patient-Reported Outcome Measure Of The Functional Impact Of Essential Tremor On Activities Of Daily Living, Ludy C Shih, Michael T Stevenson, Steven Bellows, Alfonso Fasano, Sheng-Han Kuo, Kelly E Lyons, Henry Moore, Holly A Shill, Aparna Wagle Shukla, Carlos Singer, Rodger J Elble

Faculty, Staff and Students Publications

BACKGROUND: The Essential Tremor Rating Assessment Scale (TETRAS) is a popular scale for essential tremor (ET), but its activities of daily living (ADL) and performance (P) subscales are based on a structured interview and physical exam. No patient-reported outcome (PRO) scale for ET has been developed according to US regulatory guidelines.

OBJECTIVE: Develop and validate a TETRAS PRO subscale.

METHODS: Fourteen items, rated 0-4, were derived from TETRAS ADL and structured cognitive interviews of 18 ET patients. Convergent validity analyses of TETRAS PRO versus TETRAS ADL, TETRAS-P, and the Quality of Life in Essential Tremor Questionnaire (QUEST) were computed for …

Nucleus Accumbens Core Single Cell Ensembles Bidirectionally Respond To Experienced Versus Observed Aversive Events, Oyku Dinckol, Noah Harris Wenger, Jennifer E Zachry, Munir Gunes Kutlu

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Fear learning is a critical feature of survival skills among mammals. In rodents, fear learning manifests itself through direct experience of the aversive event or social transmission of aversive stimuli such as observing and acting on conspecifics' distress. The neuronal network underlying the social transmission of information largely overlaps with the brain regions that mediate behavioral responses to aversive and rewarding stimuli. In this study, we recorded single cell activity patterns of nucleus accumbens (NAc) core neurons using in vivo optical imaging of calcium transients via miniature scopes. This cutting-edge imaging methodology not only allows us to record activity patterns …

Detection Of Prions In The Urine Of Patients Affected By Sporadic Creutzfeldt-Jakob Disease, M Talke

Faculty, Staff and Student Publications

Objective

Currently, it is unknown whether infectious prions are present in peripheral tissues and biological fluids of patients affected by sporadic Creutzfeldt–Jakob disease (sCJD), the most common prion disorder in humans. This represents a potential risk for inter‐individual prion infection. The main goal of this study was to evaluate the presence of prions in urine of patients suffering from the major subtypes of sCJD.

Methods

Urine samples from sCJD patients spanning the six major subtypes were tested. As controls, we used urine samples from people affected by other neurological or neurodegenerative diseases as well as healthy controls. These samples were …

Capacity Assessment And Spatial Analysis Of Cervical Cancer Services In The Gambia, Meghan E Mali, Ousman Sanyang, Katherine L Harris, Justin Sorensen, Mustapha Bittaye, Jonathan Nellermoe, Raymond R Price, Edward K Sutherland

Faculty, Staff and Student Publications

Background

Cervical cancer is the most common cancer and the leading cause of cancer-related death in Gambian women. The Gambian Ministry of Health is striving to improve access to screening, diagnostic, and treatment services for cervical cancer, but comprehensive data on currently available services is limited making it challenging to appropriately prioritize the ideal next steps for expanding care. This study aims to describe the current services available for the prevention, screening, and treatment of cervical cancer in The Gambia and provide suggestions for expanding geographic access to care.

Methods

A survey aimed at assessing the availability of key cervical …

Agreement Between Published Reference Resources For Neurofilament Light Chain Levels In People With Multiple Sclerosis., Elias S Sotirchos, Chen Hu, Matthew D Smith, Hannah-Noelle Lord, Anna L Duval, Georgina Arrambide, Xavier Montalban, Katja Akgün, Tjalf Ziemssen, Robert T Naismith, Carrie M Hersh, Megan Hyland, Lauren B Krupp, Jacqueline A Nicholas, Robert A Bermel, Ellen M Mowry, Peter A Calabresi, Kathryn C Fitzgerald

Neuroscience Articles

OBJECTIVES: To examine the agreement between published reference resources for neurofilament light chain (NfL) applied to a large population of people with multiple sclerosis (MS).

METHODS: Six published reference resources were used to classify NfL in participants in the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) network as elevated or normal and to derive age-specific NfL

RESULTS: NfL measurements were assessed from 12,855 visits of 6,687 people with MS (median 2 samples per individual [range 1-7]). The mean ± SD age was 47.1 ± 11.7 years, 72.1% of participants were female, disease duration was 15.0 ± 10.6 …