Neurology Commons^™

Theta Burst Brain Stimulation In Painful Diabetic Neuropathy Patients: Investigating Neural Mechanisms, Bhushan Thakkar

Theses and Dissertations

Chronic pain (CP) is a significant contributor to disability and disease burden globally. In 2019, approximately 50.2 million adults (20.4% of the US population) experienced chronic pain, contributing to $560-635 billion in direct medical costs. In addition, the worldwide prevalence of diabetes mellitus has reached epidemic proportions and is set to increase to 629 million by 2045. Almost 50% of patients with diabetes present with diabetic neuropathy (DN), and one in five patients with diabetes presents with painful DN (pDN) which is the most common cause of neuropathic pain (NP) in the US. Symptomatic treatment is the mainstay of management …

Multi-Center, Single-Blind Randomized Controlled Trial Comparing Functional Electrical Stimulation Therapy To Conventional Therapy In Incomplete Tetraplegia, Kim D Anderson, Radha Korupolu, Kristin E Musselman, Jacqueline Pierce, James R Wilson, Nuray Yozbatiran, Naaz Desai, Milos R Popovic, Lehana Thabane

Faculty, Staff and Student Publications

BACKGROUND: Loss of upper extremity function after tetraplegia results in significant disability. Emerging evidence from pilot studies suggests that functional electrical stimulation (FES) therapy may enhance recovery of upper extremity function after tetraplegia. The aim of this trial was to determine the effectiveness of FES therapy delivered by the Myndmove stimulator in people with tetraplegia.

METHODS: A multi-center

RESULTS: Between June 2019 to August 2021, 51 participants were randomized to FES (

CONCLUSION: Forty sessions of FES therapy delivered by the MyndMove stimulator are as effective as conventional therapy in producing meaningful functional improvements that persist after therapy is completed. …

Video Game Rehabilitation For Outpatient Stroke (Vigorous): A Multi-Site Randomized Controlled Trial Of In-Home, Self-Managed, Upper-Extremity Therapy., Lynne V Gauthier, Deborah S Nichols-Larsen, Gitendra Uswatte, Nancy Strahl, Marie Simeo, Rachel Proffitt, Kristina Kelly, Roger Crawfis, Edward Taub, David Morris, Linda Pax Lowes, Victor Mark, Alexandra Borstad

Neuroscience Articles

BACKGROUND: Integrating behavioral intervention into motor rehabilitation is essential for improving paretic arm use in daily life. Demands on therapist time limit adoption of behavioral programs like Constraint-Induced Movement (CI) therapy, however. Self-managed motor practice could free therapist time for behavioral intervention, but there remains insufficient evidence of efficacy for a self-management approach.

METHODS: This completed, parallel, five-site, pragmatic, single-blind trial established the comparative effectiveness of using in-home gaming self-management as a vehicle to redirect valuable therapist time towards behavioral intervention. Community-dwelling adults with post-stroke (>6 months) mild/moderate upper extremity hemiparesis were randomized to receive one of 4 different …

Covid-19 Outcomes In Myasthenia Gravis Patients: Analysis From Electronic Health Records In The United States, Youngran Kim, Xiaojin Li, Yan Huang, Minseon Kim, Aziz Shaibani, Kazim Sheikh, Guo-Qiang Zhang, Thy Phuong Nguyen

Faculty, Staff and Student Publications

BACKGROUND: Myasthenia gravis (MG) is an autoimmune, neuromuscular condition and patients with MG are vulnerable due to immunosuppressant use and disease manifestations of dyspnea and dysphagia during the coronavirus disease 2019 (COVID-19) pandemic.

METHODS: We conducted a retrospective cohort study using the Optum® de-identified COVID-19 Electronic Health Record (EHR) dataset. Primary outcomes, such as hospitalization, ventilator use, intensive care unit (ICU) admission, and death in COVID-19 patients with MG, were compared with those of COVID-19 patients without MG: the subgroups of non-MG included those with rheumatoid arthritis (RA), systemic lupus (SLE), and multiple sclerosis (MS). We further analyzed factors affecting …

Qu-Brats: Miccai Brats 2020 Challenge On Quantifying Uncertainty In Brain Tumor Segmentation - Analysis Of Ranking Scores And Benchmarking Results, Raghav Mehta, Angelos Filos, Ujjwal Baid, Chiharu Sako, Richard Mckinley, Michael Rebsamen, Katrin Dätwyler, Raphael Meier, Piotr Radojewski, Gowtham Krishnan Murugesan, Sahil Nalawade, Chandan Ganesh, Ben Wagner, Fang F. Yu, Baowei Fei, Ananth J. Madhuranthakam, Joseph A. Maldjian, Laura Daza, Catalina Gómez, Pablo Arbeláez, Chengliang Dai, Shuo Wang, Hadrien Reynaud, Yuan-Han Mo, Elsa Angelini, Yike Guo, Wenjia Bai, Subhashis Banerjee, Lin-Min Pei, Murat Ak, Sarahi Rosas-González, Ilyess Zemmoura, Clovis Tauber, Minh H. Vu, Tufve Nyholm, Tommy Löfstedt, Laura Mora Ballestar, Veronica Vilaplana, Hugh Mchugh, Gonzalo Maso Talou, Alan Wang, Jay Patel, Ken Chang, Katharina Hoebel, Mishka Gidwani, Nishanth Arun, Sharut Gupta, Mehak Aggarwal, Praveer Singh, Elizabeth R. Gerstner, Jayashree Kalpathy-Cramer, Nicholas Boutry, Alexis Huard, Lasitha Vidyaratne, Md. Monibor Rahman, Khan M. Iftekharuddin, Joseph Chazalon, Elodie Puybareau, Guillaume Tochon, Jun Ma, Mariano Cabezas, Xavier Llado, Arnau Oliver, Liliana Valencia, Sergi Valverde, Mehdi Amian, Mohammadreza Soltaninejad, Andriy Myronenko, Ali Hatamizadeh, Xue Feng, Quan Dou, Nicholas Tustison, Craig Meyer, Nisarg A. Shah, Sanjay Talbar, Marc-André Weber, Abhishek Mahajan, Andras Jakab, Roland Wiest, Hassan M. Fathallah-Shaykh, Arash Nazeri, Mikhail Milchenko1, Daniel Marcus, Aikaterini Kotrotsou, Rivka Colen, John Freymann, Justin Kirby, Christos Davatzikos, Bjoern Menze, Spyridon Bakas, Yarin Gal, Tal Arbel

Electrical & Computer Engineering Faculty Publications

Deep learning (DL) models have provided the state-of-the-art performance in a wide variety of medical imaging benchmarking challenges, including the Brain Tumor Segmentation (BraTS) challenges. However, the task of focal pathology multi-compartment segmentation (e.g., tumor and lesion sub-regions) is particularly challenging, and potential errors hinder the translation of DL models into clinical workflows. Quantifying the reliability of DL model predictions in the form of uncertainties, could enable clinical review of the most uncertain regions, thereby building trust and paving the way towards clinical translation. Recently, a number of uncertainty estimation methods have been introduced for DL medical image segmentation tasks. …

Blood Metabolites Predicting Mild Cognitive Impairment In The Study Of Latinos-Investigation Of Neurocognitive Aging (Hchs/So), Shan He, Einat Granot-Hershkovitz, Ying Zhang, Jan Bressler, Wassim Tarraf, Bing Yu, Tianyi Huang, Donglin Zeng, Sylvia Wassertheil-Smoller, Melissa Lamar, Martha Daviglus, Maria J Marquine, Jianwen Cai, Thomas Mosley, Robert Kaplan, Eric Boerwinkle, Myriam Fornage, Charles Decarli, Bruce Kristal, Hector M Gonzalez, Tamar Sofer

Faculty, Staff and Student Publications

INTRODUCTION: Blood metabolomics-based biomarkers may be useful to predict measures of neurocognitive aging.

METHODS: We tested the association between 707 blood metabolites measured in 1451 participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), with mild cognitive impairment (MCI) and global cognitive change assessed 7 years later. We further used Lasso penalized regression to construct a metabolomics risk score (MRS) that predicts MCI, potentially identifying a different set of metabolites than those discovered in individual-metabolite analysis.

RESULTS: We identified 20 metabolites predicting prevalent MCI and/or global cognitive change. Six of them were novel and 14 were previously reported as …

Advancements In The Quest To Map, Monitor, And Manipulate Neural Circuitry, Jessica L Swanson, Pey-Shyuan Chin, Juan M Romero, Snigdha Srivastava, Joshua Ortiz-Guzman, Patrick J Hunt, Benjamin R Arenkiel

Duncan NRI Faculty and Staff Publications

Neural circuits and the cells that comprise them represent the functional units of the brain. Circuits relay and process sensory information, maintain homeostasis, drive behaviors, and facilitate cognitive functions such as learning and memory. Creating a functionally-precise map of the mammalian brain requires anatomically tracing neural circuits, monitoring their activity patterns, and manipulating their activity to infer function. Advancements in cell-type-specific genetic tools allow interrogation of neural circuits with increased precision. This review provides a broad overview of recombination-based and activity-driven genetic targeting approaches, contemporary viral tracing strategies, electrophysiological recording methods, newly developed calcium, and voltage indicators, and neurotransmitter/neuropeptide biosensors …

Comparison Of Treadmill Gait Between A Pediatric-Aged Individual With Syngap1-Related Intellectual Disability And A Fraternal Twin, Charles S Layne, Christopher A Malaya, David R Young, Berhard Suter, Jimmy L Holder

Duncan NRI Faculty and Staff Publications

SYNGAP1-related Intellectual Disability (SYNGAP1-ID) is a rare neurodevelopmental condition characterized by profound intellectual disability, gross motor delays, and behavioral issues. Ataxia and gait difficulties are often observed but have not yet been characterized by laboratory-based kinematic analyses. This investigation identified gait characteristics of an individual with SYNGAP1-ID and compared these with a neurotypical fraternal twin. Lower limb kinematics were collected with a 12-camera motion capture system while both participants walked on a motorized treadmill. Kinematic data were separated into strides, and stride times calculated. Sagittal plane hip, knee, and ankle joints were filtered and temporally normalized …

Recurrent Liponeurocytoma: A Case Report And Systematic Review Of The Literature, Darsh S Shah, Himanshu Sharma, Prem Patel, Arya Shetty, Collin William English, J Clay Goodman, Ashwin Viswanathan, Akash J Patel

Duncan NRI Faculty and Staff Publications

Background: Liponeurocytomas are rare neurocytic neoplasms that most often arise in the posterior fossa and affect individuals in the third and fifth decades of life. Most reported cases of this unique tumor in the literature have described a favorable clinical prognosis without recurrence. However, increasing reports of recurrent cases prompted the World Health Organization, in 2016, to recategorize the tumor from Grade I to the less favorable Grade II classification. We conducted a systematic review to identify recurrent cases of this unique tumor and to summarize differences between the primary and recurrent cases of liponeurocytoma.

Methods: A systematic review exploring …

Functional Studies Of Genetic Variants Associated With Human Diseases In Notch Signaling-Related Genes Using Drosophila, Sheng-An Yang, Jose L Salazar, David Li-Kroeger, Shinya Yamamoto

Duncan NRI Faculty and Staff Publications

Rare variants in the many genes related to Notch signaling cause diverse Mendelian diseases that affect myriad organ systems. In addition, genome- and exome-wide association studies have linked common and rare variants in Notch-related genes to common diseases and phenotypic traits. Moreover, somatic mutations in these genes have been observed in many types of cancer, some of which are classified as oncogenic and others as tumor suppressive. While functional characterization of some of these variants has been performed through experimental studies, the number of ‘variants of unknown significance’ identified in patients with diverse conditions keeps increasing as high-throughput sequencing technologies …

Epithelial Morphogenesis In The Drosophila Egg Chamber Requires Parvin And Ilk, Athina Keramidioti, Evgenia Golegou, Eleni Psarra, Nikolaos Paschalidis, Konstantina Kalodimou, Shinya Yamamoto, Christos Delidakis, Katerina M Vakaloglou, Christos G Zervas

Duncan NRI Faculty and Staff Publications

Integrins are the major family of transmembrane proteins that mediate cell-matrix adhesion and have a critical role in epithelial morphogenesis. Integrin function largely depends on the indirect connection of the integrin cytoplasmic tail to the actin cytoskeleton through an intracellular protein network, the integrin adhesome. What is currently unknown is the role of individual integrin adhesome components in epithelia dynamic reorganization. Drosophila egg chamber consists of the oocyte encircled by a monolayer of somatic follicle epithelial cells that undergo specific cell shape changes. Egg chamber morphogenesis depends on a developmental array of cell-cell and cell-matrix signalling events. Recent elegant work …

Emerging Roles Of Alternative Cleavage And Polyadenylation (Apa) In Human Disease, Prakash Dharmalingam, Rajasekaran Mahalingam, Hari Krishna Yalamanchili, Tingting Weng, Harry Karmouty-Quintana, Ashrith Guha, Rajarajan A Thandavarayan

Duncan NRI Faculty and Staff Publications

In the messenger RNA (mRNA) maturation process, the 3'-end of pre-mRNA is cleaved and a poly(A) sequence is added, this is an important determinant of mRNA stability and its cellular functions. More than 60%-70% of human genes have three or more polyadenylation (APA) sites and can be cleaved at different sites, generating mRNA transcripts of varying lengths. This phenomenon is termed as alternative cleavage and polyadenylation (APA) and it plays role in key biological processes like gene regulation, cell proliferation, senescence, and also in various human diseases. Loss of regulatory microRNA binding sites and interactions with RNA-binding proteins leading to …

Uncertainty Estimation In Classification Of Mgnt Using Radiogenomics For Glioblastoma Patients, W. Farzana, Z. A. Shboul, A. Temtam, K. M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Glioblastoma Multiforme (GBM) is one of the most malignant brain tumors among all high-grade brain cancers. Temozolomide (TMZ) is the first-line chemotherapeutic regimen for glioblastoma patients. The methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) gene is a prognostic biomarker for tumor sensitivity to TMZ chemotherapy. However, the standardized procedure for assessing the methylation status of MGMT is an invasive surgical biopsy, and accuracy is susceptible to resection sample and heterogeneity of the tumor. Recently, radio-genomics which associates radiological image phenotype with genetic or molecular mutations has shown promise in the non-invasive assessment of radiotherapeutic treatment. This study proposes a machine-learning framework …

Factors Associated With Ventilator Weaning Success And Failure In People With Spinal Cord Injury In An Acute Inpatient Rehabilitation Setting: A Retrospective Study, Radha Korupolu, Hannah Uhlig-Reche, Emmanuel Chigozie Achilike, Colton Reeh, Claudia Pedroza, Argyrios Stampas

Faculty, Staff and Student Publications

OBJECTIVES: To evaluate baseline characteristics, describe pulmonary outcomes, and identify weaning predictors for people with acute traumatic spinal cord injury (SCI) who are dependent on mechanical ventilation at admission to acute inpatient rehabilitation (AIR).

METHODS: The retrospective study was conducted at an AIR facility in the United States. It included 91 adults with acute traumatic SCI from 2015 to 2019 who were dependent on mechanical ventilation.

RESULTS: People who successfully weaned (85%) had fewer days from time of SCI to AIR admission (22 vs. 30,

CONCLUSION: In this retrospective study, there was an increased risk of pneumonia in people with …

Cytokines And Chemokines Profile In Encephalitis Patients: A Meta-Analysis, Alireza Soltani Khaboushan, Mohammad-Taha Pahlevan-Fallahy, Parnian Shobeiri, Antônio L Teixeira, Nima Rezaei

Faculty, Staff and Student Publications

Background: Encephalitis is caused by autoimmune or infectious agents marked by brain inflammation. Investigations have reported altered concentrations of the cytokines in encephalitis. This study was conducted to determine the relationship between encephalitis and alterations of cytokine levels in cerebrospinal fluid (CSF) and serum.

Methods: We found possibly suitable studies by searching PubMed, Embase, Scopus, and Web of Science, systematically from inception to August 2021. 23 articles were included in the meta-analysis. To investigate sources of heterogeneity, subgroup analysis and sensitivity analysis were conducted. The protocol of the study has been registered in PROSPERO with a registration ID of CRD42021289298. …

Digital Rehabilitation For Hand And Wrist Pain: A Single-Arm Prospective Longitudinal Cohort Study, Fabíola Costa, Dora Janela, Maria Molinos, Robert G Moulder, Jorge Lains, Gerard E Francisco, Virgílio Bento, Vijay Yanamadala, Steven P Cohen, Fernando Dias Correia

Faculty, Staff and Student Publications

Introduction: Wrist and hand represent the third most common body part in work-related injuries, being associated with long-term absenteeism. Telerehabilitation can promote access to treatment, patient adherence, and engagement, while reducing health care-related costs.

Objective: Report the results of a fully remote digital care program (DCP) for wrist and hand pain (WP).

Methods: A single-arm interventional study was conducted on individuals with WP applying for a DCP. Primary outcome was the mean change in the Numerical Pain Rating Scale after 8 weeks (considering a minimum clinically important change of 30%). Secondary outcomes were: disability (Quick Disabilities of the Arm, Shoulder, …

Mri Free Water As A Biomarker For Cognitive Performance: Validation In The Markvcid Consortium, Pauline Maillard, Laura J Hillmer, Hanzhang Lu, Konstantinos Arfanakis, Brian T Gold, Christopher E Bauer, Joel H Kramer, Adam M Staffaroni, Lara Stables, Danny J J Wang, Sudha Seshadri, Claudia L Satizabal, Alexa Beiser, Mohamad Habes, Myriam Fornage, Thomas H Mosley, Gary A Rosenberg, Baljeet Singh, Herpreet Singh, Kristin Schwab, Karl G Helmer, Steven M Greenberg, Charles Decarli, Arvind Caprihan

Faculty, Staff and Student Publications

Introduction: To evaluate the clinical validity of free water (FW), a diffusion tensor imaging-based biomarker kit proposed by the MarkVCID consortium, by investigating the association between mean FW (mFW) and executive function.

Methods: Baseline mFW was related to a baseline composite measure of executive function (EFC), adjusting for relevant covariates, in three MarkVCID sub-cohorts, and replicated in five, large, independent legacy cohorts. In addition, we tested whether baseline mFW predicted accelerated EFC score decline (mean follow-up time: 1.29 years).

Results: Higher mFW was found to be associated with lower EFC scores in MarkVCID legacy and sub-cohorts (p-values < 0.05). In addition, higher baseline mFW was associated significantly with accelerated decline in EFC scores (p …