Neurology Commons^™

From Covid-19 To Long Covid; The Forms Of The Neurological Manifestations, Sana Ahuja, Sufian Zaheer

Journal of Mind and Medical Sciences

Ever since the SARS-CoV-2 infection was declared a global pandemic in 2020, numerous multisystemic manifestations have been discovered. The COVID-19 is known to cause a wide spectrum of neurological symptoms like fatigue, headache, brain fog, stroke, smell and taste disorders, encephalopathy and neurodegenerative disorders. The neurological manifestations are more prevalent in the post-COVID syndrome or long COVID. The National Institute for Health and Care Excellence and WHO defined Ongoing Symptomatic COVID as 4-12 weeks post infection and post COVID-19 syndrome as persistence of symptoms beyond 12 weeks. So far there are limited data available regarding the pathophysiology of neurological symptoms …

Ciprofloxacin-Induced Peripheral Neuropathy: A Case Report, Alexander Refaeian, Eric L. Vest, Michael Schmidt, Jorge D. Guerra, Mohd N. Refaei, Michael Refaeian, Ryan A. Floresca, Manouchehr Refaeian

HCA Healthcare Journal of Medicine

Introduction

Fluoroquinolones, a class of antibiotics, are commonly employed in the treatment of a wide array of bacterial infections. Recognized for their effectiveness against a broad spectrum of pathogens, fluoroquinolones have played a pivotal role in managing conditions like urinary tract infections and respiratory diseases. Nevertheless, their usage is not without contention due to their association with a variety of adverse effects, including tendon rupture and the less frequently reported issue of peripheral neuropathy.

Case Presentation

We present the case of a 42-year-old male who developed peripheral neuropathy several days after completing a 10-day course of ciprofloxacin for gastroenteritis. The …

Caregiver Perspectives On The Daily Function Of People Living With Hnrnph2-Related Neurodevelopmental Disorder: Developing A Conceptual Model, Rachel Salazar

Seton Hall University Dissertations and Theses (ETDs)

Introduction: Neurodevelopmental disorders are a group of conditions that start in childhood and lead to impairments in functioning. HNRNPH2-related neurodevelopmental disorder is an ultra-rare disorder in which individuals present with cognitive, behavioral, language and motor function impairments that often leads to reliance on their caregivers. Existing conceptual models of neurodevelopment are not specific to this ultra rare disorder and do not highlight the caregiver impact of living with HNRNPH2-related neurodevelopmental disorder.

Purpose: The purpose of this study is to understand the caregiver perspective on the everyday functioning of people living with HNRNPH2-related neurodevelopmental disorder to generate a …

Autosomal Dominant Optic Atrophy Plus Syndrome, Aaron W. Case Od, Lovelee E. Sayomac Od, Matthew J. Anderson Od

Optometric Clinical Practice

Background: Dominant optic atrophy (DOA) is the most commonly encountered hereditary optic neuropathy in clinical practice and is the result of a mutation in the OPA1 or OPA3 genes encoding mitochondrial membrane proteins. The resultant mitochondrial dysfunction causes a distinct set of ophthalmic findings and may progress to extra-ocular systems known as OPA plus syndrome. We present a case of late-onset OPA plus syndrome encompassing both typical ophthalmic findings and the rarer extra-ocular findings. Case Report: A 41 year-old Caucasian male presents for a second opinion regarding a previously diagnosed traumatic optic neuropathy. Examination revealed decreased best-corrected acuities, …

Rna-Based Translation Activators For Targeted Gene Upregulation, Yang Cao, Huachun Liu, Shannon S Lu, Krysten A Jones, Anitha P Govind, Okunola Jeyifous, Christine Q Simmons, Negar Tabatabaei, William N Green, Jimmy L Holder, Soroush Tahmasebi, Alfred L George, Bryan C Dickinson

Duncan NRI Faculty and Staff Publications

Technologies capable of programmable translation activation offer strategies to develop therapeutics for diseases caused by insufficient gene expression. Here, we present "translation-activating RNAs" (taRNAs), a bifunctional RNA-based molecular technology that binds to a specific mRNA of interest and directly upregulates its translation. taRNAs are constructed from a variety of viral or mammalian RNA internal ribosome entry sites (IRESs) and upregulate translation for a suite of target mRNAs. We minimize the taRNA scaffold to 94 nucleotides, identify two translation initiation factor proteins responsible for taRNA activity, and validate the technology by amplifying SYNGAP1 expression, a haploinsufficiency disease target, in patient-derived cells. …

Apple Crispr-Cas9-A Recipe For Successful Targeting Of Agamous-Like Genes In Domestic Apple, Seth Jacobson, Natalie Bondarchuk, Thy Anh Nguyen, Allison Canada, Logan Mccord, Timothy S Artlip, Philipp Welser, Amy L Klocko

Faculty, Staff and Student Publications

Fruit trees and other fruiting hardwood perennials are economically valuable, and there is interest in developing improved varieties. Both conventional breeding and biotechnology approaches are being utilized towards the goal of developing advanced cultivars. Increased knowledge of the effectiveness and efficiency of biotechnology approaches can help guide use of the CRISPR gene-editing technology. Here, we examined CRISPR-Cas9-directed genome editing in the valuable commodity fruit tree Malus x domestica (domestic apple). We transformed two cultivars with dual CRISPR-Cas9 constructs designed to target two AGAMOUS-like genes simultaneously. The main goal was to determine the effectiveness of this approach for achieving target …

Methyl-Branched Liposomes As A Depot For Sustained Drug Delivery, Yang Li, Rachelle Shao, Claire A Ostertag-Hill, Matthew Torre, Ran Yan, Daniel S Kohane

Duncan NRI Faculty and Staff Publications

Inadequate drug loading and control of payload leakage limit the duration of the effect of liposomal drug carriers and may cause toxicity. Here, we report a liposome system as a depot for sustained drug delivery whose design is inspired by the low permeability of Archaeal membranes to protons and solutes. Incorporating methyl-branched phospholipids into lipid bilayers decreased payload diffusion across liposomal membranes, thereby enhancing the drug load capacity by 10-16% and reducing the release of small molecules in the first 24 h by 40-48%. The in vivo impact of this approach was demonstrated by injection at the sciatic nerve. Methyl-branched …

White Matter Integrity Abnormalities In Healthy Overweight Individuals Revealed By Whole Brain Meta-Analysis Of Diffusion Tensor Imaging Studies, Xiaodong Cheng, Wenchang Wang, Chen Sun, Yana Sun, Cong Zhou

Faculty, Staff and Student Publications

OBJECTIVE: This study aimed to conduct a coordinate-based meta-analysis (CBMA) to investigate white matter (WM) abnormalities in healthy individuals with overweight or obesity.

METHODS: A systematic literature search using Web of Science and PubMed datasets was performed. Original investigations that used diffusion tensor imaging (DTI) to explore fractional anisotropy (FA) differences between healthy overweight/obese individuals and normal weight controls were collected. The meta-analysis was conducted using the seed-based

RESULTS: The analysis included five studies comprising 232 overweight/obese individuals and 219 healthy normal weight controls. The findings showed that overweight/obese individuals exhibited reduced fractional anisotropy (FA) in specific regions, namely, the …

Early Resveratrol Treatment Mitigates Joint Degeneration And Dampens Pain In A Mouse Model Of Pseudoachondroplasia (Psach), Jacqueline T Hecht, Alka C Veerisetty, Debabrata Patra, Mohammad G Hossain, Frankie Chiu, Claire Mobed, Francis H Gannon, Karen L Posey

Faculty, Staff and Student Publications

Pseudoachondroplasia (PSACH), a severe dwarfing condition associated with early-onset joint degeneration and lifelong joint pain, is caused by mutations in cartilage oligomeric matrix protein (COMP). The mechanisms underlying the mutant-COMP pathology have been defined using the MT-COMP mouse model of PSACH that has the common D469del mutation. Mutant-COMP protein does not fold properly, and it is retained in the rough endoplasmic reticulum (rER) of chondrocytes rather than being exported to the extracellular matrix (ECM), driving ER stress that stimulates oxidative stress and inflammation, driving a self-perpetuating cycle. CHOP (ER stress signaling protein) and TNFα inflammation drive high levels of mTORC1 …

Neuroprotective Activity Of Enantiomers Of Salsolinol And N-Methyl-(R)-Salsolinol: In Vitro And In Silico Studies, Magdalena Kurnik-Łucka, Gniewomir Latacz, Adam Bucki, Mario Rivera-Meza, Nadia Khan, Jahnobi Konwar, Kamil Skowron, Marcin Kołaczkowski, Krzysztof Gil

Faculty, Staff and Student Publications

Salsolinol (1-methyl-1,2,3,4-tetrahydroisoquinoline-6,7-diol) is a close structural analogue of dopamine with an asymmetric center at the C1 position, and its presence in vivo, both in humans and rodents, has already been proven. Yet, given the fact that salsolinol colocalizes with dopamine-rich regions and was first detected in the urine of Parkinson's disease patients, its direct role in the process of neurodegeneration has been proposed. Here, we report that

Acute Aseptic Meningoencephalitis Due To Covid-19 In An Otherwise Healthy Patient: A Case Report, Shyama Appareddy, Norma Moncayo, Ronkino T. Mccoy, Jared Sperling, George Huddleston, Raza L. Kahn

Research Colloquium

Several studies have shown the extrapulmonary manifestations of COVID-19 disease caused by the SARS-CoV2 virus. Although extrapulmonary manifestation to the heart, kidney, blood, and skin are common, neurological and cerebrovascular manifestations are rare with most of these cases being described in patients who also have the pulmonary manifestation of the disease. Here we present the case of an 18 year-old male with no prior history of respiratory symptoms who presented to the emergency department with altered mental status. Neurology was consulted and the patient was started empirical on ceftriaxone, vancomycin, dexamethasone, and acyclovir for meningoencephalitis. Urine drug screen, head CT, …

A Puzzling Case Of Glutamic Acid Decarboxylase 65 (Gad65) Neurologic Syndrome, Areeb Masood, Nina Appareddy, Raul Tovar Castro, Zan Shareef, Laura Garcia

Research Colloquium

Autoimmune encephalitis (AE) is a rare group of neurological disorders in which antibodies are directed against intracellular or surface antigens. The incidence of AE ranged from between 0.4-1.2 per 100,000 person-years between 1995 and 2015. A subset of these autoimmune encephalitides that target glutamic acid decarboxylase (GAD) are termed anti-GAD related neurological disorders. GAD is the rate-limiting enzyme involved in the synthesis of GABA from glutamate, and is expressed in neurons of the cerebral cortex, cerebellum, and hippocampus. In addition, it is found in the B-islets of the pancreas, epithelial cells of the fallopian tube, and spermatocytes of the testes. …

Cd13 Facilitates Immune Cell Migration And Aggravates Acute Injury But Promotes Chronic Post-Stroke Recovery, Justin N Nguyen, Eric C Mohan, Gargee Pandya, Uzma Ali, Chunfeng Tan, Julia K Kofler, Linda Shapiro, Sean P Marrelli, Anjali Chauhan

Faculty, Staff and Student Publications

Introduction

Acute stroke leads to the activation of myeloid cells. These cells express adhesion molecules and transmigrate to the brain, thereby aggravating injury. Chronically after stroke, repair processes, including angiogenesis, are activated and enhance post-stroke recovery. Activated myeloid cells express CD13, which facilitates their migration into the site of injury. However, angiogenic blood vessels which play a role in recovery also express CD13. Overall, the specific contribution of CD13 to acute and chronic stroke outcomes is unknown.

Methods

CD13 expression was estimated in both mice and humans after the ischemic stroke. Young (8–12 weeks) male wild-type and global CD13 knockout …

Social Determinants Of Health And Disparate Disability Accumulation In A Cohort Of Black, Hispanic, And White Patients With Multiple Sclerosis, Michael C Robertson, Brian Downer, Paul E Schulz, Rafael Samper-Ternent, Elizabeth J Lyons, Sadaf Arefi Milani

Faculty, Staff and Student Publications

OBJECTIVES: Mexico has a rapidly aging population at risk for cognitive impairment. Social and leisure activities may protect against cognitive decline in older adults. The benefits of these behaviors may vary by patterns of cognitive impairment. The objectives of this study were to identify latent states of cognitive functioning, model the incidence of transitions between these states, and investigate how social and leisure activities were associated with state transitions over a 6-year period in Mexican adults aged 60 and older.

METHODS: We performed latent transition analyses to identify distinct cognitive statuses in the 2012 and 2018 waves of the Mexican …

Stabilizing Peri-Stent Restenosis Using A Novel Therapeutic Carrier, Maria P Blasco Conesa, Frank W Blixt, Pedram Peesh, Romeesa Khan, Janelle Korf, Juneyoung Lee, Gayathri Jagadeesan, Alexander Andersohn, Tushar K Das, Chunfeng Tan, Claudia Di Gesu, Gabriela Delevati Colpo, Jose Félix Moruno-Manchón, Louise D Mccullough, Robert Bryan, Bhanu P Ganesh

Faculty, Staff and Student Publications

Stroke is the most common cause of long-term disability and places a high economic burden on the global healthcare system. Functional outcomes from stroke are largely determined by the extent of ischemic injury, however, there is growing recognition that systemic inflammatory responses also contribute to outcomes. Mast cells (MCs) rapidly respond to injury and release histamine (HA), a pro-inflammatory neurotransmitter that enhances inflammation. The gut serves as a major reservoir of HA. We hypothesized that cromolyn, a mast cell stabilizer that prevents the release of inflammatory mediators, would decrease peripheral and central inflammation, reduce MC trafficking to the brain, and …

Covid-19 As A Second Hit For Anti-Phospholipid Syndrome, Himabindu Kolli, Pooja Maknoor, Celin Rajan, Nevin Varghese

Research Colloquium

Background: Anti-phospholipid syndrome (APS) is an autoimmune disorder characterized by venous and arterial thrombosis, usually in setting of underlying autoimmune disorders. Here, we present a case of anti-phospholipid syndrome post covid infection.

Case Presentation: 41-year-old lady presented to the ER with complaints of left sided facial droop for 3-day duration. On further evaluation, she was found to have subacute ischemic stroke and was managed with anticoagulation and supportive treatment. Past medical history is significant for a recent diagnosis of Covid infection and for subsequent development of lower extremity deep vein thrombosis (DVT). She was started on anticoagulation with rivaroxaban for …

Autoimmune Encephalitis Of Unknown Etiology, Elizabeth Cook, Giselle Ricoy

Research Colloquium

Encephalitis is the inflammation of the brain which can come about through various etiologies. Autoimmune encephalitis is a rare form that is most common among women and children. The clinical presentation can vary between patients with a constellation of symptoms including deficits in memory, cognition, seizures, abnormal movement, psychosis, and coma. Because of the variation in clinical presentation and the lack of specificity in imaging and laboratory findings, diagnosis and intervention are often delayed for months to years. These delays in diagnosis can have long term ramifications on patients especially pediatric patients whose neural pathways are still developing. In pediatric …

Subacute Stroke In Young Hispanic Male With Vertebrobasilar Dolichoectasia, Ashika A. Chacko, Nevin A. Varghese

Research Colloquium

Background: Vertebrobasilar dolichoectasia (VBD) is a rare clinical entity characterized by dilatation, elongation, and tortuosity of the vertebrobasilar arteries. Patients with VBD can present varying symptoms from ischemia, compression of blood vessels, or rarely subarachnoid hemorrhage.

Case presentation: A 29-year-old Hispanic man with history of hypertension presented to emergency department with progressive left upper extremity weakness, dizziness, slurry speech, and diplopia of one-week duration. On arrival, the patient was afebrile, heart rate 75 bpm and blood pressure 193/107 mmHg. He was alert and oriented x3. Neurological exam demonstrated decreased strength (4/5) on left upper extremity and left arm pronator drift. …

Comparative Genomic Landscape Of Urothelial Carcinoma Of The Bladder Among Patients Of East And South Asian Genomic Ancestry, Taylor Peak, Philippe E Spiess, Roger Li, Petros Grivas, Andrea Necchi, Dean Pavlick, Richard S P Huang, Douglas Lin, Natalie Danziger, Joseph M Jacob, Gennady Bratslavsky, Jeffrey S Ross

Faculty, Staff and Student Publications

BACKGROUND: Despite the low rate of urothelial carcinoma of the bladder (UCB) in patients of South Asian (SAS) and East Asian (EAS) descent, they make up a significant portion of the cases worldwide. Nevertheless, these patients are largely under-represented in clinical trials. We queried whether UCB arising in patients with SAS and EAS ancestry would have unique genomic features compared to the global cohort.

METHODS: Formalin-fixed, paraffin-embedded tissue was obtained for 8728 patients with advanced UCB. DNA was extracted and comprehensive genomic profiling was performed. Ancestry was classified using a proprietary calculation algorithm. Genomic alterations (GAs) were determined using a …

Clinical Genome Sequencing: Three Years’ Experience At A Tertiary Children’S Hospital, Runjun D Kumar, Lisa F Saba, Haley Streff, Chad A Shaw, Elizabeth Mizerik, Matthew T Snyder, Dolores Lopez-Terrada, Jennifer Scull

Duncan NRI Faculty and Staff Publications

Purpose: Genome sequencing (GS) may shorten the diagnostic odyssey for patients, but clinical experience with this assay in nonresearch settings remains limited. Texas Children's Hospital began offering GS as a clinical test to admitted patients in 2020, providing an opportunity to study GS utilization, possibilities for test optimization, and testing outcomes.

Methods: We retrospectively reviewed GS orders for admitted patients for a nearly 3-year period from March 2020 through December 2022. We gathered anonymized clinical data from the electronic health record to answer the study questions.

Results: The diagnostic yield over 97 admitted patients was 35%. The majority of GS …