Neurology Commons^™

The Uprmt Preserves Mitochondrial Import To Extend Lifespan, Jolaade Kalinowski, Elizabeth A Hintz, Chigozirim Izeogu

Faculty, Staff and Student Publications

The SARS-CoV-2 (COVID-19) pandemic introduced many challenges and nuances that have transformed medical practice and research. The uncertainty caused by COVID-19 led to inevitable challenges to patient-provider relationships. The ever-changing landscape of COVID-19 research and policy proved to be challenging for the medical community and patients. These challenges also exacerbated long-standing issues regarding patient-provider communication and trust. On the other hand, these challenges gave voice to a burgeoning patient advocacy community. Through social media, advocacy and patient organizing, patients harnessed their power and organized over challenges relating to COVID-19 fears and concerns, ramifications of "Long COVID," and much more. During …

Association Of Circulating Ketone Bodies With Cognitive Performance And Dementia In The Multi-Ethnic Study Of Atherosclerosis (Mesa), Parag Anilkumar Chevli, Christopher L Schaich, Alexis C Wood, Luqman A Tk, Anurag Mehta, Vardhmaan Jain, Margery Connelly, Suzanne Craft, Elad Shemesh, José A Luchsinger, Kathleen M Hayden, Bonnie Colleen Sachs, Timothy M Hughes, Michael D Shapiro

Faculty, Staff and Students Publications

Introduction

Growing interest centers on the association between circulating ketone bodies (KB) and cognitive function, notably in aging and neurodegenerative diseases.

Methods

Associations of plasma KB with incident dementia and cognitive performances were examined among Multi‐Ethnic Study of Atherosclerosis (MESA) participants. KB were measured using plasma samples collected following an overnight fasting at Exam 1 (2000–02) and detailed cognitive testing at Exam 5 (2010–2012, N = 4392), Exam 6 (2016–2018, N = 1838), and in MESA‐MIND (2019–2021, N = 2060).

Results

Over 16.7 years, a doubling of total KB was associated with a greater risk of incident dementia (hazard ratio …

De Novo Missense Variants In Zbtb47 Are Associated With Developmental Delays, Hypotonia, Seizures, Gait Abnormalities, And Variable Movement Abnormalities, Scott K Ward, Alexandrea Wadley, Chun-Hui Anne Tsai, Paul J Benke, Lisa Emrick, Kristen Fisher, Kimberly M Houck, Hongzheng Dai, Undiagnosed Diseases Network, Maria J Guillen Sacoto, William Craigen, Kimberly Glaser, David R Murdock, Luis Rohena, Karin E M Diderich, Hennie T Bruggenwirth, Brendan Lee, Carlos Bacino, Lindsay C Burrage, Jill A Rosenfeld

Faculty, Staff and Students Publications

The collection of known genetic etiologies of neurodevelopmental disorders continues to increase, including several syndromes associated with defects in zinc finger protein transcription factors (ZNFs) that vary in clinical severity from mild learning disabilities and developmental delay to refractory seizures and severe autism spectrum disorder. Here we describe a new neurodevelopmental disorder associated with variants in ZBTB47 (also known as ZNF651), which encodes zinc finger and BTB domain-containing protein 47. Exome sequencing (ES) was performed for five unrelated patients with neurodevelopmental disorders. All five patients are heterozygous for a de novo missense variant in ZBTB47, with p.(Glu680Gly) (c.2039A>G) detected …

Tremor In Cervical Dystonia, Sinem Balta Beylergil, Krishna Nikhil Mukunda, Mohamed Elkasaby, Joel S Perlmutter, Stewart Factor, Tobias Bäumer, Jeanne Feurestein, Erika Shelton, Steven Bellows, Joseph Jankovic, Abhimanyu Mahajan, Tila Wamer-Rosen, Stephen G Reich, Aparna Wagle Shukla, Irene Malaty, Alberto Espay, Kevin Duque, Mark S Ledoux, Rachel Saunders-Pullman, Katherine Leaver, Samuel Frank, Alexander Pantelyat, Victor Fung, Sarah Pirio Richardson, Brian Berman, Natividad Stover, Andres Deik, William Ondo, Christopher Groth, Hyder A Jinnah, Aasef G Shaikh

Faculty, Staff and Students Publications

BACKGROUND: Cervical dystonia (CD) is the most common form of focal dystonia encountered in the clinic. Approximately one-third of CD patients have co-existing tremor in the head and hands. Assessment of tremor as regular or irregular in context of its oscillation trajectory, frequency, and amplitude is a major clinical challenge and can confound the diagnosis of CD. The misdiagnosis may lead to therapeutic failures, poor quality of life, and poor utilization of medical and financial resources.

METHODS: We analyzed the largest cohort of CD patients (

RESULTS: Out of 3,117 CD patients, 1,367 had neck tremor. The neck tremor was …

Use Of Botulinum Toxin In The Management Of Dystonia In Parkinson’S Disease, Charenya Anandan, Joseph Jankovic

Faculty, Staff and Students Publications

Botulinum toxin is one of the most potent neurotoxins, but when injected into an overactive muscle, it can transiently alleviate an involuntary movement, such as dystonia. The primary aim of this article is to provide a comprehensive review of the various forms of dystonia observed in patients with Parkinson's disease who can benefit from a therapeutic trial of botulinum toxin. Although most of these indications are not supported by randomized controlled clinical trials and, therefore, not approved by the Food and Drug Administration, there are many open-label trials supporting a large body of empirical experience testifying to the benefits of …

Ultradian Rhythms In Accelerometric And Autonomic Data Vary Based On Seizure Occurrence In Paediatric Epilepsy Patients, Solveig Vieluf, Sarah Cantley, Vaishnav Krishnan, Tobias Loddenkemper

Faculty, Staff and Students Publications

Ultradian rhythms are physiological oscillations that resonate with period lengths shorter than 24 hours. This study examined the expression of ultradian rhythms in patients with epilepsy, a disease defined by an enduring seizure risk that may vary cyclically. Using a wearable device, we recorded heart rate, body temperature, electrodermal activity and limb accelerometry in patients admitted to the paediatric epilepsy monitoring unit. In our case–control design, we included recordings from 29 patients with tonic–clonic seizures and 29 non-seizing controls. We spectrally decomposed each signal to identify cycle lengths of interest and compared average spectral power- and period-related markers between groups. …

Screening For Adhd In Adult Patients With Epilepsy: Prevalence Of Symptoms And Challenges To Diagnosis, Trung Nguyen, Emily Xiao, Allison Clark, Afroz Shamim, Atul Maheshwari

Faculty, Staff and Students Publications

OBJECTIVE: Given the complex nature of seizure disorders and their treatments, ADHD may be underdiagnosed in this population. We hypothesized that a higher percentage of patients presenting to a seizure clinic would endorse ADHD symptoms compared to rates reported in the general population and that formal screening for ADHD symptoms would identify patients with previously undiagnosed comorbid ADHD.

METHODS: In this study, we surveyed 312 adults in a seizure clinic using the Adult ADHD Self-Report Scale (ASRS-v1.1).

RESULTS: We found that 90 patients (28.8%) screened positive with the ASRS-v1.1, but only nine of these patients were able to complete neuropsychological …

Continuous Subcutaneous Foslevodopa/Foscarbidopa Infusion For The Treatment Of Motor Fluctuations In Parkinson’S Disease: Considerations For Initiation And Maintenance, Victor S C Fung, Jason Aldred, Martha P Arroyo, Filip Bergquist, Agnita J W Boon, Manon Bouchard, Sarah Bray, Sara Dhanani, Maurizio F Facheris, Nahome Fisseha, Eric Freire-Alvarez, Robert A Hauser, Anna Jeong, Jia Jia, Pavnit Kukreja, Michael J Soileau, Amy M Spiegel, Saritha Talapala, Arjun Tarakad, Enrique Urrea-Mendoza, Jorge Zamudio, Rajesh Pahwa

Faculty, Staff and Students Publications

BACKGROUND: As Parkinson's disease (PD) advances, management is challenged by an increasingly variable and inconsistent response to oral dopaminergic therapy, requiring special considerations by the provider. Continuous 24 h/day subcutaneous infusion of foslevodopa/foscarbidopa (LDp/CDp) provides steady dopaminergic stimulation that can reduce symptom fluctuation.

OBJECTIVE: Our aim is to review the initiation, optimization, and maintenance of LDp/CDp therapy, identify possible challenges, and share potential mitigations.

METHODS: Review available LDp/CDp clinical trial data for practical considerations regarding the management of patients during LDp/CDp therapy initiation, optimization, and maintenance based on investigator clinical trial experience.

RESULTS: LDp/CDp initiation, optimization, and maintenance can be …

A Dual Target Molecular Magnetic Resonance Imaging Probe For Noninvasive Profiling Of Pathologic Alpha-Synuclein And Microgliosis In A Mouse Model Of Parkinson’S Disease, Xianwei Sun, Andrew Badachhape, Prajwal Bhandari, Jeannie Chin, Ananth Annapragada, Eric Tanifum

Faculty, Staff and Students Publications

The pathogenesis of Parkinson’s disease (PD) is characterized by progressive deposition of alpha-synuclein (α-syn) aggregates in dopaminergic neurons and neuroinflammation. Noninvasive in vivo imaging of α-syn aggregate accumulation and neuroinflammation can elicit the underlying mechanisms involved in disease progression and facilitate the development of effective treatment as well as disease diagnosis and prognosis. Here we present a novel approach to simultaneously profile α-syn aggregation and reactive microgliosis in vivo, by targeting oligomeric α-syn in cerebrospinal fluid with nanoparticle bearing a magnetic resonance imaging (MRI), contrast payload. In this proof-of-concept report we demonstrate, in vitro, that microglia and neuroblastoma …

Night-Time Neuronal Activation Of Cluster N In A North American Songbird\, Jennifer Rudolf, Natalie Philipello, Tamara Fleihan, J David Dickman, Kira E Delmore

Faculty, Staff and Students Publications

Night-migrating songbirds utilize the Earth's magnetic field to help navigate to and from their breeding sites each year. A region of the avian forebrain called Cluster N has been shown to be activated during night migratory behavior and it has been implicated in processing geomagnetic information. Previous studies with night-migratory European songbirds have shown that neuronal activity at Cluster N is higher at night than during the day. Comparable work in North American migrants has only been performed in one species of swallows, so extension of examination for Cluster N in other migratory birds is needed. In addition, it is …

Cisplatin Vestibulotoxicity: A Current Review, Tamara Fleihan, Marc Elie Nader, J David Dickman

Faculty, Staff and Students Publications

Cisplatin, a commonly used chemotherapy drug, is well-established for its ototoxic effects, primarily attributed to the damage it inflicts on cochlear hair cells. However, its impact on the vestibular system remains inadequately understood. Here, we provide a comprehensive review of existing literature concerning cisplatin-induced vestibulotoxicity. Animal studies have shown that cisplatin induces a vestibular hair cell loss that is dose-dependent, with the severity of damage also varying according to the route of administration. Notably, intratympanic and systemic injections in animal models have manifested significant damage primarily to utricular hair cells, with a lesser degree of damage observed for the other …

Translational Symmetry In Convolutions With Localized Kernels Causes An Implicit Bias Toward High Frequency Adversarial Examples, Josue O Caro, Yilong Ju, Ryan Pyle, Sourav Dey, Wieland Brendel, Fabio Anselmi, Ankit B Patel

Faculty, Staff and Students Publications

Adversarial attacks are still a significant challenge for neural networks. Recent efforts have shown that adversarial perturbations typically contain high-frequency features, but the root cause of this phenomenon remains unknown. Inspired by theoretical work on linear convolutional models, we hypothesize that translational symmetry in convolutional operations together with localized kernels implicitly bias the learning of high-frequency features, and that this is one of the main causes of high frequency adversarial examples. To test this hypothesis, we analyzed the impact of different choices of linear and non-linear architectures on the implicit bias of the learned features and adversarial perturbations, …

Scan-Less Microscopy Based On Acousto-Optic Encoded Illumination, Andrea Marchese, Pietro Ricci, Peter Saggau, Martí Duocastella

Faculty, Staff and Students Publications

Several optical microscopy methods are now available for characterizing scientific and industrial processes at sub-micron resolution. However, they are often ill-suited for imaging rapid events. Limited by the trade-off between camera frame-rate and sensitivity, or the need for mechanical scanning, current microscopes are optimized for imaging at hundreds of frames-per-second (fps), well-below what is needed in processes such as neuronal signaling or moving parts in manufacturing lines. Here, we present a scan-less technology that allows sub-micrometric imaging at thousands of fps. It is based on combining a single-pixel camera with parallelized encoded illumination. We use two acousto-optic deflectors (AODs) placed …

Thrombectomy In Stroke Patients With Low Alberta Stroke Program Early Computed Tomography Score: Is Modified Thrombolysis In Cerebral Infarction (Mtici) 2c/3 Superior To Mtici 2b?, Sameh Samir Elawady, Brian Fabian Saway, Hidetoshi Matsukawa, Kazutaka Uchida, Steven Lin, Ilko Maier, Pascal Jabbour, Joon-Tae Kim, Stacey Quintero Wolfe, Ansaar Rai, Robert M Starke, Marios-Nikos Psychogios, Edgar A Samaniego, Adam Arthur, Shinichi Yoshimura, Hugo Cuellar, Jonathan A Grossberg, Ali Alawieh, Daniele G Romano, Omar Tanweer, Justin Mascitelli, Isabel Fragata, Adam Polifka, Joshua Osbun, Roberto Crosa, Charles Matouk, Min S Park, Michael R Levitt, Waleed Brinjikji, Mark Moss, Travis Dumont, Richard Williamson, Pedro Navia, Peter Kan, Reade De Leacy, Shakeel Chowdhry, Mohamad Ezzeldin, Alejandro M Spiotta, Sami Al Kasab

Faculty, Staff and Students Publications

BACKGROUND AND PURPOSE: Outcomes following mechanical thrombectomy (MT) are strongly correlated with successful recanalization, traditionally defined as modified Thrombolysis in Cerebral Infarction (mTICI) ≥2b. This retrospective cohort study aimed to compare the outcomes of patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS; 2-5) who achieved mTICI 2b versus those who achieved mTICI 2c/3 after MT.

METHODS: This study utilized data from the Stroke Thrombectomy and Aneurysm Registry (STAR), which combined databases from 32 thrombectomy-capable stroke centers between 2013 and 2023. The study included only patients with low ASPECTS who achieved mTICI 2b, 2c, or 3 after MT …

Proceedings Of The 11th Annual Deep Brain Stimulation Think Tank: Pushing The Forefront Of Neuromodulation With Functional Network Mapping, Biomarkers For Adaptive Dbs, Bioethical Dilemmas, Ai-Guided Neuromodulation, And Translational Advancements, Kara A Johnson, Nico U F Dosenbach, Evan M Gordon, Cristin G Welle, Kevin B Wilkins, Helen M Bronte-Stewart, Valerie Voon, Takashi Morishita, Yuki Sakai, Amanda R Merner, Gabriel Lázaro-Muñoz, Theresa Williamson, Andreas Horn, Ro'ee Gilron, Jonathan O'Keeffe, Aryn H Gittis, Wolf-Julian Neumann, Simon Little, Nicole R Provenza, Sameer A Sheth, Alfonso Fasano, Abbey B Holt-Becker, Robert S Raike, Lisa Moore, Yagna J Pathak, David Greene, Sara Marceglia, Lothar Krinke, Huiling Tan, Hagai Bergman, Monika Pötter-Nerger, Bomin Sun, Laura Y Cabrera, Cameron C Mcintyre, Noam Harel, Helen S Mayberg, Andrew D Krystal, Nader Pouratian, Philip A Starr, Kelly D Foote, Michael S Okun, Joshua K Wong

Faculty, Staff and Students Publications

The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9-11, 2023 in Gainesville, Florida with the theme of "Pushing the Forefront of Neuromodulation". The keynote speaker was Dr. Nico Dosenbach from Washington University in St. Louis, Missouri. He presented his research recently published in Nature inn a collaboration with Dr. Evan Gordon to identify and characterize the somato-cognitive action network (SCAN), which has redefined the motor homunculus and has led to new hypotheses about the integrative networks underpinning therapeutic DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers, and …

Multimodal Prediction Of Obsessive-Compulsive Disorder And Comorbid Depression Severity And Energy Delivered By Deep Brain Electrodes, Saurabh Hinduja, Ali Darzi, Itir Onal Ertugrul, Nicole Provenza, Ron Gadot, Eric A Storch, Sameer A Sheth, Wayne K Goodman, Jeffrey F Cohn

Faculty, Staff and Students Publications

To develop reliable, valid, and efficient measures of obsessive-compulsive disorder (OCD) severity, comorbid depression severity, and total electrical energy delivered (TEED) by deep brain stimulation (DBS), we trained and compared random forests regression models in a clinical trial of participants receiving DBS for refractory OCD. Six participants were recorded during open-ended interviews at pre- and post-surgery baselines and then at 3-month intervals following DBS activation. Ground-truth severity was assessed by clinical interview and self-report. Visual and auditory modalities included facial action units, head and facial landmarks, speech behavior and content, and voice acoustics. Mixed-effects random forest regression with Shapley feature …

Delivering Multidisciplinary Rehabilitation Care In Parkinson's Disease: An International Consensus Statement, Jennifer G Goldman, Daniele Volpe, Terry D Ellis, Mark A Hirsch, Julia Johnson, Julia Wood, Ana Aragon, Roberta Biundo, Alessandro Di Rocco, Glenn S Kasman, Robert Iansek, Janis Miyasaki, Victor M Mcconvey, Marten Munneke, Serge Pinto, Karen A St Clair, Santiago Toledo, Michele K York, Ronnie Todaro, Nicole Yarab, Kristin Wallock

Faculty, Staff and Students Publications

BACKGROUND: Parkinson's disease (PD) is a complex neurodegenerative disorder impacting everyday function and quality of life. Rehabilitation plays a crucial role in improving symptoms, function, and quality of life and reducing disability, particularly given the lack of disease-modifying agents and limitations of medications and surgical therapies. However, rehabilitative care is under-recognized and under-utilized in PD and often only utilized in later disease stages, despite research and guidelines demonstrating its positive effects. Currently, there is a lack of consensus regarding fundamental topics related to rehabilitative services in PD.

OBJECTIVE: The goal of the international Parkinson's Foundation Rehabilitation Medicine Task Force was …

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 …

Multiple Sclerosis In Central America And Caribbean Countries: Frequency And Clinical Characterization Of An Emergent Disease, Fernando Gracia, Deyanira A Ramírez Navarro, Nicia E Ramírez Sánchez, Roberto Weiser, Alexander Parajeles-Vindas, Ligia I Portillo Rivera, Ericka López Torres, Luis A García Valle, Alfredo Sanabria-Castro, César Abdón López, Pahola Araujo, Maria J Ayerdis Zamora, Andrea Balmaceda-Meza, Aron Benzadon Cohen, Awilda Candelario Cueto, Diego Castillo, Romy Castro-Escobar, Karla Z Corea Urbina, Anyeri De Peña Rivas, Octavio Duarte Sotelo, Temís Enamorado Claros, José L Giroud Benítez, Karla Gracia, Mario Larreategui, Jorge A Martínez Cerrato, Josmarlin P Medina Báez, Carlos E Menjivar Samayoa, Gustavo Miranda-Loria, Priscilla Monterrey-Alvarez, Lilliam A Morales Arguello, Michelle Ortiz, Carlos D Pérez Baldioceda, Lizeth Pinilla Aguilar, Luis C Rodríguez Salinas, Virginia Rodríguez-Moreno, Sebastián Rojas-Chaves, Norbel Román-Garita, Biany Santos Pujols, Carlos Valderrama, Ivonne Van Sijtveld, Indhira Zabala Angeles, Victor M Rivera, Blas Armien

Faculty, Staff and Students Publications

BACKGROUND: Multiple Sclerosis (MS) is a common neurological disease among white populations of European origin. Frequencies among Latin Americans continue to be studied, however, epidemiologic, and clinical characterization studies lack from Central American and Caribbean countries. Ethnicity in these countries is uniformly similar with a prevalent Mestizo population.

METHODS AND RESULTS: Data from January 2014 to December 2019 from Guatemala, El Salvador, Honduras, Nicaragua, Costa Rica, Panama, Dominican Republic, and Aruba on demographic, clinical, MRI and phenotypic traits were determined in coordinated studies: ENHANCE, a population-based, retrospective, observational study on incidence and clinical characteristics, and from the subgroup with MS …

Para-Infectious Brain Injury In Covid-19 Persists At Follow-Up Despite Attenuated Cytokine And Autoantibody Responses, Benedict D Michael, Cordelia Dunai, Edward J Needham, Kukatharmini Tharmaratnam, Robyn Williams, Yun Huang, Sarah A Boardman, Jordan J Clark, Parul Sharma, Krishanthi Subramaniam, Greta K Wood, Ceryce Collie, Richard Digby, Alexander Ren, Emma Norton, Maya Leibowitz, Soraya Ebrahimi, Andrew Fower, Hannah Fox, Esteban Tato, Mark A Ellul, Geraint Sunderland, Marie Held, Claire Hetherington, Franklyn N Egbe, Alish Palmos, Kathy Stirrups, Alexander Grundmann, Anne-Cecile Chiollaz, Jean-Charles Sanchez, James P Stewart, Michael Griffiths, Tom Solomon, Gerome Breen, Alasdair J Coles, Nathalie Kingston, John R Bradley, Patrick F Chinnery, Jonathan Cavanagh, Sarosh R Irani, Angela Vincent, J Kenneth Baillie, Peter J Openshaw, Malcolm G Semple, Covid-Cns Consortium, Isaric4c Investigators, Leonie S Taams, David K Menon

Faculty, Staff and Student Publications

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1-11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common …

Education Research: Virtual Patient Management Conference For Epilepsy Surgery In The Post-Covid-19 Era: An Educational Perspective, Thomas Pecha, Sharonya Shetty, Abhishek Kengen, Jay Gavvala, Atul Maheshwari

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: The primary objective of this study was to assess the potential educational value of a virtual patient management conference (PMC) with the introduction of inclusive anonymous polling at a comprehensive epilepsy center. The secondary objective was to evaluate differences between faculty and trainee polling results.

METHODS: Two online surveys were sent 1 year apart seeking opinions about a transition to virtual PMC and completed by virtual PMC faculty participants (including representatives from neurology, neurosurgery, and neuropsychology). One online survey was sent to trainees (medical students, residents, and fellows) to assess the educational value of the conference. Anonymous …

Mirna-211 Maintains Metabolic Homeostasis In Medulloblastoma Through Its Target Gene Long-Chain Acyl-Coa Synthetase 4, Menglang Yuan, Iqbal Mahmud, Keisuke Katsushima, Kandarp Joshi, Olivier Saulnier, Rudramani Pokhrel, Bongyong Lee, Wathsala Liyanage, Haritha Kunhiraman, Stacie Stapleton, Ignacio Gonzalez-Gomez, Rangaramanujam M Kannan, Tanja Eisemann, Elayaraja Kolanthai, Sudipta Seal, Timothy J Garrett, Saed Abbasi, Kimberly Bockley, Justin Hanes, Prem Chapagain, George Jallo, Robert J Wechsler-Reya, Michael D Taylor, Charles G Eberhart, Animesh Ray, Ranjan J Perera

Faculty, Staff and Students Publications

The prognosis of childhood medulloblastoma (MB) is often poor, and it usually requires aggressive therapy that adversely affects quality of life. microRNA-211 (miR-211) was previously identified as an important regulator of cells that descend from neural cells. Since medulloblastomas primarily affect cells with similar ontogeny, we investigated the role and mechanism of miR-211 in MB. Here we showed that miR-211 expression was highly downregulated in cell lines, PDXs, and clinical samples of different MB subgroups (SHH, Group 3, and Group 4) compared to normal cerebellum. miR-211 gene was ectopically expressed in transgenic cells from MB subgroups, and they were subjected …

Isoform-Level Transcriptome-Wide Association Uncovers Genetic Risk Mechanisms For Neuropsychiatric Disorders In The Human Brain, Arjun Bhattacharya, Daniel D Vo, Connor Jops, Minsoo Kim, Cindy Wen, Jonatan L Hervoso, Bogdan Pasaniuc, Michael J Gandal

Faculty, Staff and Student Publications

Methods integrating genetics with transcriptomic reference panels prioritize risk genes and mechanisms at only a fraction of trait-associated genetic loci, due in part to an overreliance on total gene expression as a molecular outcome measure. This challenge is particularly relevant for the brain, in which extensive splicing generates multiple distinct transcript-isoforms per gene. Due to complex correlation structures, isoform-level modeling from cis-window variants requires methodological innovation. Here we introduce isoTWAS, a multivariate, stepwise framework integrating genetics, isoform-level expression and phenotypic associations. Compared to gene-level methods, isoTWAS improves both isoform and gene expression prediction, yielding more testable genes, and increased power …

Word Reading, Reading Comprehension, And Eye Movements During Reading In Chinese Persons With Aphasia, Xiaobin Wang

Graduate Theses and Dissertations (2019 - present)

Individuals with aphasia (IWA) often exhibit challenges in single word reading as well as in reading comprehension. Recently, eye-tracking technology has become instrumental in delving deeper into reading behaviors. Specifically, it has illuminated the differences in word reading and comprehension abilities among aphasic English speakers. However, there is a noticeable scarcity of research focusing on these aspects among Chinese IWA. The current study aimed to contrast the abilities of Chinese IWA and neurotypical controls in reading single words, with an emphasis on types like regular, irregular, and pseudowords, and reading comprehension abilities. Further, this study investigated the patterns of eye …

Huntington Study Group's Neuropsychology Working Group: Implementing Non-Motor Diagnostic Criteria, Ciaran M Considine, M Agustina Rossetti, Victor A Del Bene, Kendra Anderson, Sharlet A Anderson, Andrea S Celka, Mary C Edmondson, Amelia L Nelson-Sheese, Adam Piccolino, Antonio L Teixeira, Julie C Stout

Faculty, Staff and Student Publications

Background: The clinical diagnosis of manifest Huntington's disease (HD) relies on a high level of clinical confidence (99% confidence) of HD-consistent motor signs. Longitudinal data have reliably identified cognitive and behavioral dysfunction predating clinical motor diagnosis by up to 15 years. Reliance on motor signs to establish a diagnosis of HD increases risk of early misdiagnosis or delayed diagnosis. Clinical neuropsychologists are uniquely positioned to advise on the clinical application of the Movement Disorder Society Task Force's recently proposed non-motor diagnostic criteria for HD.

Objectives: To provide (1) a recommended clinical approach toward non-motor diagnostic criteria in persons with HD …

Cortical Thickness Is Related To Variability In Heritage Bilingual Language Proficiency, My V H Nguyen, Kelly A Vaughn, Hannah Claussenius-Kalman, Pilar Archila-Suerte, Arturo E Hernandez

Faculty, Staff and Student Publications

Research suggests that bilingual experience is associated with gray matter changes, such that initial language gains are associated with expansion and language expertise is associated with renormalization. Previous studies on language proficiency development primarily focused on between-subjects, quasiexperimental comparisons of monolinguals and bilinguals. This study proposes a new paradigm to examine language expertise and cortical thickness within heritage bilinguals (

Behavioral Or Neuropsychiatric Symptoms Of Alzheimer’S Disease: From Psychopathology To Pharmacological Management, Antonio Lucio Teixeira, Natalia Pessoa Rocha, Jennifer Gatchel

Faculty, Staff and Student Publications

Neuropsychiatric or behavioral symptoms of dementia encompass a series of disorders, such as anxiety, depression, apathy, psychosis, and agitation, all commonly present in individuals living with dementia. While they are not required for the diagnosis of Alzheimer's disease (AD), they are ubiquitously present in all stages of the disease, contributing to negative clinical outcomes, including cognitive decline, functional disability, and caregiver burden. Neuropsychiatric symptoms have been conceptualized not only as risk factors but as clinical markers of decline along the AD spectrum. The concept of "mild behavioral impairment", the behavioral correlate of mild cognitive impairment, has been proposed within this …

Radiographic And Clinical Outcomes With Particle Or Liquid Embolic Agents For Middle Meningeal Artery Embolization Of Nonacute Subdural Hematomas, Jonathan P Scoville, Evan Joyce, Daniel A Tonetti, Michael T Bounajem, Ajith Thomas, Christopher S Ogilvy, Justin M Moore, Howard A Riina, Omar Tanweer, Elad I Levy, Alejandro M Spiotta, Bradley A Gross, Brian T Jankowitz, C Michael Cawley, Alexander A Khalessi, Aditya S Pandey, Andrew J Ringer, Ricardo Hanel, Rafael A Ortiz, David Langer, Michael R Levitt, Mandy Binning, Philipp Taussky, Peter Kan, Ramesh Grandhi

Faculty, Staff and Students Publications

BACKGROUND: Middle meningeal artery (MMA) embolization is an apparently efficacious minimally invasive treatment for nonacute subdural hematomas (NASHs), but how different embolisates affect outcomes remains unclear. Our objective was to compare radiographic and clinical outcomes after particle or liquid MMA embolization.

METHODS: Patients who had MMA embolization for NASH were retrospectively identified from a multi-institution database. The primary radiographic and clinical outcomes-50% NASH thickness reduction and need for surgical retreatment within 90 days, respectively-were compared for liquid and particle embolizations in patients treated 1) without surgical intervention (upfront), 2) after recurrence, or 3) with concomitant surgery (prophylactic).

RESULTS: The upfront, …

Management Strategies Of Unanticipated Intracranial Stenosis During Mechanical Thrombectomy For Acute Stroke: A Survey Of Academic Neurointerventionalists, Tyler T Lazaro, Alex N Hoang, Patrick C Cotton, Huy Q Dang, Omar Tanweer, Daniel M S Raper

Faculty, Staff and Students Publications

BACKGROUND: The optimal approach to the management of intracranial atherosclerotic disease (ICAD) at the time of mechanical thrombectomy (MT) for large vessel occlusion (LVO) remains controversial. The goal of this study is to characterize current practices concerning this challenging clinical situation in a survey of practicing neurointerventionalists.

METHODS: An electronic questionnaire was sent to a cross-section of North American academic neurointerventionalists using publicly available contact information and departmental websites. Prior to analysis, responses were anonymized and categorized by region.

RESULTS: A total of 136/360 responses were recorded from the U.S. and Canada. The mean number of years of practicing as …

Computer Vision In Osteoporotic Vertebral Fracture Risk Prediction: A Systematic Review, Anthony K Allam, Adrish Anand, Alex R Flores, Alexander E Ropper

Faculty, Staff and Students Publications

Osteoporotic vertebral fractures (OVFs) are a significant health concern linked to increased morbidity, mortality, and diminished quality of life. Traditional OVF risk assessment tools like bone mineral density (BMD) only capture a fraction of the risk profile. Artificial intelligence, specifically computer vision, has revolutionized other fields of medicine through analysis of videos, histopathology slides and radiological scans. In this review, we provide an overview of computer vision algorithms and current computer vision models used in predicting OVF risk. We highlight the clinical applications, future directions and limitations of computer vision in OVF risk prediction.