Neurology Commons^™

Cd11bhigh B Cells Increase After Stroke And Regulate Microglia: Cd11bhigh B Cells Increase After Stroke And Regulate Mg, Janelle M Korf, Pedram Honarpisheh, Eric C Mohan, Anik Banerjee, Maria P Blasco-Conesa, Parisa Honarpisheh, Gary U Guzman, Romeesa Khan, Bhanu P Ganesh, Amy L Hazen, Juneyoung Lee, Aditya Kumar, Louise D Mccullough, Anjali Chauhan

Faculty, Staff and Student Publications

Recent studies have highlighted the deleterious contributions of B cells to post-stroke recovery and cognitive decline. Different B cell subsets have been proposed based on expression levels of transcription factors (e.g. T-bet) as well as specific surface proteins. CD11b (α-chain of integrin) is expressed by several immune cell types and is involved in regulation of cell motility, phagocytosis, and other essential functions of host immunity. Although B cells express CD11b, the CD11b^high subset of B cells has not been well characterized, especially in immune dysregulation seen with aging and after stroke. Here, we investigate the role of CD11b^{high …}

Renin-Angiotensin System In Huntington's Disease: Evidence From Animal Models And Human Patients, Lucas M Kangussu, Natalia P Rocha, Priscila A C Valadão, Thatiane C G Machado, Kívia B Soares, Julliane V Joviano-Santos, Leigh B Latham, Gabriela D Colpo, Ana Flávia Almeida-Santos, Erin Furr Stimming, Ana Cristina Simões E Silva, Antônio L Teixeira, Aline Silva Miranda, Cristina Guatimosim

Faculty, Staff and Student Publications

The Renin-Angiotensin System (RAS) is expressed in the central nervous system and has important functions that go beyond blood pressure regulation. Clinical and experimental studies have suggested that alterations in the brain RAS contribute to the development and progression of neurodegenerative diseases. However, there is limited information regarding the involvement of RAS components in Huntington's disease (HD). Herein, we used the HD murine model, (BACHD), as well as samples from patients with HD to investigate the role of both the classical and alternative axes of RAS in HD pathophysiology. BACHD mice displayed worse motor performance in different behavioral tests alongside …

Small Rna Signatures Of Acute Ischemic Stroke In L1cam Positive Extracellular Vesicles, Michael A Lopez, Ying Si, Xianzhen Hu, Valentyna Williams, Fuad Qushair, Jackson Carlyle, Lyndsy Alesce, Michael Conklin, Shawn Gilbert, Marcas M Bamman, Matthew S Alexander, Peter H King

Faculty, Staff and Student Publications

Duchenne muscular dystrophy (DMD) is an X-linked recessive disease characterized by skeletal muscle instability, progressive muscle wasting, and fibrosis. A major driver of DMD pathology stems from aberrant upregulation of transforming growth factor β (TGFβ) signaling. In this report, we investigated the major transducers of TGFβ signaling, i.e., receptor Smads (R-Smads), in DMD patient skeletal muscle and observed a 48-fold increase in Smad8 mRNA. Smad1, Smad2, Smad3, and Smad5 mRNA were only minimally increased. A similar pattern was observed in the muscle from the mdx5cv mouse. Western blot analysis showed upregulation of phosphorylated Smad1, Smad5, and Smad8 …

Evaluation Of A Process Change Using An Updated Sedation Protocol, Rachel Allen

Dissertations

Problem: Pediatric delirium is continuing to increase intensive care environments and for patients who require mechanical ventilation and continuous sedative medications. Delirium is harmful to the patient creating lasting neurologic and mental health issues along with prolonged hospitalization and increased healthcare cost

Method: For this quality improvement (QI) project, a descriptive observational study was used to evaluate the implementation of a sedation protocol for patients who are mechanically ventilated and on continuous sedative medications. This was completed with the use of retrospective chart reviews three months prior to implementation and three months after the new protocol was implemented. Nurses were …

Gene-Based Therapeutics For Rare Genetic Neurodevelopmental Psychiatric Disorders, Beverly L Davidson, Guangping Gao, Elizabeth Berry-Kravis, Allison M Bradbury, Carsten Bönnemann, Joseph D Buxbaum, Gavin R Corcoran, Steven J Gray, Heather Gray-Edwards, Robin J Kleiman, Adam J Shaywitz, Dan Wang, Huda Y Zoghbi, Terence R Flotte, Sitra Tauscher-Wisniewski, Cynthia J Tifft, Mustafa Sahin

Duncan NRI Faculty and Staff Publications

We are in an emerging era of gene-based therapeutics with significant promise for rare genetic disorders. The potential is particularly significant for genetic central nervous system disorders that have begun to achieve Food and Drug Administration approval for select patient populations. This review summarizes the discussions and presentations of the National Institute of Mental Health-sponsored workshop "Gene-Based Therapeutics for Rare Genetic Neurodevelopmental Psychiatric Disorders," which was held in January 2021. Here, we distill the points raised regarding various precision medicine approaches related to neurodevelopmental and psychiatric disorders that may be amenable to gene-based therapies.

Macrophage Migration Inhibitory Factor (Mif) Makes Complex Contributions To Pain-Related Hyperactivity Of Nociceptors After Spinal Cord Injury, Alexis Bavencoffe, Emily A Spence, Michael Y Zhu, Anibal Garza-Carbajal, Kerry E Chu, Ona E Bloom, Carmen W Dessauer, Edgar T Walters

Faculty, Staff and Student Publications

Neuropathic pain is a major, inadequately treated challenge for people with spinal cord injury (SCI). While SCI pain mechanisms are often assumed to be in the CNS, rodent studies have revealed mechanistic contributions from primary nociceptors. These neurons become chronically hyperexcitable after SCI, generating ongoing electrical activity that promotes ongoing pain. A major question is whether extrinsic chemical signals help to drive ongoing electrical activity after SCI. People living with SCI exhibit acute and chronic elevation of circulating levels of macrophage migration inhibitory factor (MIF), a cytokine implicated in preclinical pain models. Probable nociceptors isolated from male rats and exposed …

Pilot Study For Correlation Of Heart Rate Variability And Dopamine Transporter Brain Imaging In Patients With Parkinsonian Syndrome, Devdutta S Warhadpande, Jiayan Huo, William A Libling, Carol Stuehm, Bijan Najafi, Scott Sherman, Hong Lei, Janet Meiling Roveda, Phillip H Kuo

Center on Aging Staff Publications

Background: Parkinsonian syndrome (PS) is a broad category of neurodegenerative movement disorders that includes Parkinson disease, multiple system atrophy (MSA), progressive supranuclear palsy, and corticobasal degeneration. Parkinson disease (PD) is the second most common neurodegenerative disorder with loss of dopaminergic neurons of the substantia nigra and, thus, dysfunction of the nigrostriatal pathway. In addition to the motor symptoms of bradykinesia, rigidity, tremors, and postural instability, nonmotor symptoms such as autonomic dysregulation (AutD) can also occur. Heart rate variability (HRV) has been used as a measure of AutD and has shown to be prognostic in diseases such as diabetes mellitus and …

Transcription Factor Runx3 Mediates Plasticity Of Thgm Cells Toward Th1 Phenotype, Javad Rasouli, Giacomo Casella, Weifeng Zhang, Dan Xiao, Gaurav Kumar, Paolo Fortina, Guang-Xian Zhang, Bogoljub Ciric, Abdolmohamad Rostami

Department of Neurology Faculty Papers

GM-CSF-producing T helper (Th) cells play a crucial role in the pathogenesis of autoimmune diseases such as multiple sclerosis (MS). Recent studies have identified a distinct population of GM-CSF-producing Th cells, named ThGM cells, that also express cytokines TNF, IL-2, and IL-3, but lack expression of master transcription factors (TF) and signature cytokines of commonly recognized Th cell lineages. ThGM cells are highly encephalitogenic in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Similar to Th17 cells, in response to IL-12, ThGM cells upregulate expression of T-bet and IFN-γ and switch their phenotype to Th1. Here we show that …

Stroke Care: Achieving Recommended Door To Computed Tomography Times In Ambulatory Patients Presenting To The Emergency Department Of A Rural Hospital Through The Application Of American Stroke Association Guidelines, Ricardo Paitz

Doctor of Nursing Practice Projects

Background: Time matters in stroke care, and every second counts because the extent of irreversible neuronal damage increases over time (Saver, 2006). Therefore, the American Stroke Association (ASA) recommends a door to computed tomography time of 20 minutes or less for patients presenting with signs of acute ischemic stroke. This time metric in stroke care is often not met, resulting in the delay of care of patients which translates to poorer outcomes, including death and a decreased quality of life in patients who have suffered an acute ischemic stroke (Kamal, Sheng, et al., 2017).

Purpose: The purpose of this DNP …

Limbic And Paralimbic Respiratory Modulation: From Inhibition To Enhancement, Ganne Chaitanya, Johnson P Hampson, Emilia Toth, Norma J Hupp, Jaison S Hampson, John C Mosher, Sandipan Pati, Samden D Lhatoo, Nuria Lacuey

Faculty, Staff and Student Publications

Objective: Increased understanding of the role of cortical structures in respiratory control may help the understanding of seizure-induced respiratory dysfunction that leads to sudden unexpected death in epilepsy (SUDEP). The aim of this study was to characterize respiratory responses to electrical stimulation (ES), including inhibition and enhancement of respiration.

Methods: We prospectively recruited 19 consecutive patients with intractable epilepsy undergoing stereotactic electroencephalography (EEG) evaluation from June 2015 to June 2018. Inclusion criteria were patients ≥18 years in whom ES was indicated for clinical mapping of ictal onset or eloquent cortex as part of the presurgical evaluation. ES was carried out …

A Randomized, Double-Blind Trial Of Triheptanoin For Drug-Resistant Epilepsy In Glucose Transporter 1 Deficiency Syndrome, Pasquale Striano, Stéphane Auvin, Abigail Collins, Rita Horvath, Ingrid E Scheffer, Michal Tzadok, Ian Miller, Mary Kay Koenig, Adrian Lacy, Ronald Davis, Angela Garcia-Cazorla, Russell P Saneto, Melanie Brandabur, Susan Blair, Tony Koutsoukos, Darryl De Vivo

Faculty, Staff and Student Publications

Objective: This study was undertaken to evaluate efficacy and long-term safety of triheptanoin in patients >1 year old, not on a ketogenic diet, with drug-resistant seizures associated with glucose transporter 1 deficiency syndrome (Glut1DS).

Methods: UX007G-CL201 was a randomized, double-blind, placebo-controlled trial. Following a 6-week baseline period, eligible patients were randomized 3:1 to triheptanoin or placebo. Dosing was titrated to 35% of total daily calories over 2 weeks. After an 8-week placebo-controlled period, all patients received open-label triheptanoin through Week 52.

Results: The study included 36 patients (15 children, 13 adolescents, eight adults). A median 12.6% reduction in overall seizure …

Contributions Of Semantic And Phonological Working Memory To Narrative Language Independent Of Single Word Production: Evidence From Acute Stroke, Rachel Zahn, Tatiana T Schnur, Randi C Martin

Faculty, Staff and Student Publications

Neuropsychological case studies have provided evidence that individuals with semantic, but not phonological, working memory (WM) deficits have difficulty producing phrases containing several content words. These findings supported the claim of a phrasal scope of planning at the grammatical formulation stage of production, where semantic WM supports the maintenance of lexical-semantic representations as they are inserted into slots in phrasal constituents. Recent narrative production results for individuals at the acute stage of stroke supported the role for semantic WM in phrasal elaboration while suggesting a role for phonological WM at a subsequent phonological encoding stage in supporting fluent, rapid speech. …

Telerounding: A Scoping Review And Implications For Future Healthcare Practice, Natasha N Ludwig, Amanda E Child, Dasal Tenzin Jashar, Allison J Mostow, Ericka L Wodka

Faculty, Staff and Student Publications

A diagnosis of autism spectrum disorder (ASD) provides access to interventions that are important for fostering development and improving quality of life. Thus, the timeliness of a diagnosis should not be limited by social-distancing limitations whenever possible. Despite this, clear guidance for transitioning autism diagnostic services to a telehealth model of care in the era of the COVID-19 pandemic is lacking. At our Institute, we have adapted our approach to ASD evaluation to promote continued access to evaluation services during this unprecedented time. The purpose of this case series is to provide examples of three different approaches to ASD differential …

Elimination Of Pseudo-Hfos In Ieeg Using Sparse Representation And Random Forest Classifier, Behrang Fazli Besheli, Zhiyi Sha, Thomas Henry, Jay R Gavvala, Candan Gurses, Sacit Karamursel, Nuri F Ince

Faculty, Staff and Student Publications

High-Frequency Oscillation (HFO) is a promising biomarker of the epileptogenic zone. However, sharp artifacts might easily pass the conventional HFO detectors as real HFOs and reduce the seizure onset zone (SOZ) localization. We hypothesize that, unlike pseudo-HFOs, which originates from artifacts with sharp changes or arbitrary waveform characteristic, real HFOs could be represented by a limited number of oscillatory waveforms. Accordingly, to distinguish true ones from pseudo-HFOs, we established a new classification method based on sparse representation of candidate events that passed an initial detector with high sensitivity but low specificity. Specifically, using the Orthogonal Matching Pursuit (OMP) and a …

Tfeb Induces Mitochondrial Itaconate Synthesis To Suppress Bacterial Growth In Macrophages, Ev-Marie Schuster, Maximilian W Epple, Katharina M Glaser, Michael Mihlan, Kerstin Lucht, Julia A Zimmermann, Anna Bremser, Aikaterini Polyzou, Nadine Obier, Nina Cabezas-Wallscheid, Eirini Trompouki, Andrea Ballabio, Jörg Vogel, Joerg M Buescher, Alexander J Westermann, Angelika S Rambold

Duncan NRI Faculty and Staff Publications

Successful elimination of bacteria in phagocytes occurs in the phago-lysosomal system, but also depends on mitochondrial pathways. Yet, how these two organelle systems communicate is largely unknown. Here we identify the lysosomal biogenesis factor transcription factor EB (TFEB) as regulator for phago-lysosome-mitochondria crosstalk in macrophages. By combining cellular imaging and metabolic profiling, we find that TFEB activation, in response to bacterial stimuli, promotes the transcription of aconitate decarboxylase (Acod1, Irg1) and synthesis of its product itaconate, a mitochondrial metabolite with antimicrobial activity. Activation of the TFEB-Irg1-itaconate signalling axis reduces the survival of the intravacuolar pathogen Salmonella enterica serovar Typhimurium. TFEB-driven …

Primary Middle Meningeal Artery Embolization For A Chronic Subdural Hematoma After Non-Accidental Trauma In A Child: A Case Report, Saisree Ravi, Sohum Desai, Ameer E. Hassan, Wondwossen G. Tekle

School of Medicine Publications

Chronic subdural hematoma in children can be pathognomonic of abusive head trauma. Treatment options for these range from observation to surgical evacuation depending on clinical circumstance and presenting features, which can include mental status changes, headaches, focal neurologic deficits, or asymptomatic presentation. Standalone endovascular treatments represent an area of growing interest in the adult population as an effective treatment modality. However, embolization as a singular treatment approach has not been reported in the pediatric population. We report the first case of stand-alone middle meningeal artery (MMA) embolization of a chronic subdural hematoma as a sequela of abusive head trauma in …

Podium Presentation: Spontaneous Intraventricular Empyema In A Patient With Bacterial Sinusitis, Rachel Freedberg, Brian J. Carlson, Cynthia Murphy, Teresa Bigand

2022 Providence Nurse Research Conference

No abstract provided.

The Modified Rankin Scale Can Accurately Be Derived From The Electronic Medical Record, Derek Isenberg, Nelson Prus, Frederick Ramsey, Nina T. Gentile

Transformative Medicine

Abstract

Introduction

The modified Rankin Scale (mRS) is used to assess functional outcomes after a stroke and is the primary outcome in many stroke trials. For retrospective stroke research or stroke research in which patients are lost to study follow up, review of the electronic medical record (EMR) may be the sole way to estimate a patient’s functional outcome. The purpose of this study is to determine if a mRS can be accurately derived from the electronic medical record EMR.

Methods

This study used data from completed stroke studies in which in-person 90-day mRS were collected as part of the …

Brain Functional Topology Differs By Sex In Cognitively Normal Older Adults, Zhengshi Yang, Filippo Cieri, Jefferson W. Kinney, Jeffrey L. Cummings, Dietmar Cordes, Jessica Z K Caldwell

Brain Health Faculty Research

Introduction: Late onset Alzheimer’s disease (AD) is the most common form of dementia, in which almost 70% of patients are women. Hypothesis: We hypothesized that women show worse global FC metrics compared to men, and further hypothesized a sex-specific positive correlation between FC metrics and cognitive scores in women. Methods: We studied cognitively healthy individuals from the Alzheimer’s Disease Neuroimaging Initiative cohort, with resting-state functional Magnetic Resonance Imaging. Metrics derived from graph theoretical analysis and functional connectomics were used to assess the global/regional sex differences in terms of functional integration and segregation, considering the amyloid status and the contributions of …

Transmission, Strain Diversity, And Zoonotic Potential Of Chronic Wasting Disease, Sandra Pritzkow

Faculty, Staff and Student Publications

Chronic wasting disease (CWD) is a prion disease affecting several species of captive and free-ranging cervids. In the past few decades, CWD has been spreading uncontrollably, mostly in North America, resulting in a high increase of CWD incidence but also a substantially higher number of geographical regions affected. The massive increase in CWD poses risks at several levels, including contamination of the environment, transmission to animals cohabiting with cervids, and more importantly, a putative transmission to humans. In this review, I will describe the mechanisms and routes responsible for the efficient transmission of CWD, the strain diversity of natural CWD, …