Nervous System Diseases Commons^™

The Treatment Of Depression In Alzheimer's Disease Using Neuromodulation: A Literature Review, Aaron Marbn, Shane Ragland, Thalia Adrian, Clara Alvarez Villalba, Samuel Neuhut

East Florida Division GME Research Day 2023

Please see supplemental content for full abstract with references.

INTRODUCTION: An estimated 44 million individuals live with Alzheimer's Dementia globally, a number expected to triple by 2050.1 Depression is a commonly observed comorbidity in individuals with Alzheimer's disease. Traditional antidepressant medications often pose challenges due to their side effects and limited efficacy in this population. As a result, alternative therapeutic approaches are being explored, with Transcranial Magnetic Stimulation (TMS) emerging as a promising intervention for treating depression in Alzheimer's patients. TMS is a non-invasive brain stimulation technique that utilizes magnetic fields to modulate neural activity in targeted brain regions …

Precision Medicine Approach To Alzheimer’S Disease: Rationale And Implications, Dale E. Bredesen, Kat Toups, Ann Hathaway, Deborha Gordon, Henrianna Chung, Cyrus Raji, Alan Boyd, Benjamin D. Hill, Sharon Hausman-Cohen, Mouna Attarha, Won Jong Chwa, Alexei Kurakin, Michael Jarrett

University Faculty and Staff Publications

The neurodegenerative disease field has enjoyed extremely limited success in the development of effective therapeutics. One potential reason is the lack of disease models that yield accurate predictions and optimal therapeutic targets. Standard clinical trials have pre-determined a single treatment modality, which may be unrelated to the primary drivers of neurodegeneration. Recent proof-of-concept clinical trials using a precision medicine approach suggest a new model of Alzheimer’s disease (AD) as a chronic innate encephalitis that creates a network insufficiency. Identifying and addressing the multiple potential contributors to cognitive decline for each patient may represent a more effective strategy. Here we review …

Evaluation Of Cold Atmospheric Plasma For The Decontamination Of Flexible Endoscopes, R. C. Hervé, Michael G. Kong, Sudhir Bhatt, Hai-Lan Chen, E. E. Comoy, J-P. Deslys, T. J. Secker, C. W. Keevil

Bioelectrics Publications

Background: Despite adherence to standard protocols, residues including live microorganisms may remain on the various surfaces of reprocessed flexible endoscopes. Prions are infectious proteins notoriously difficult to eliminate.

Aim: We tested the potential of cold atmospheric plasma (CAP) for the decontamination of flexible endoscope various surfaces, measuring total proteins and prion-residual infectivity as an indicator of efficacy.

Methods: New PTFE endoscope channels and metal test surfaces spiked with test soil or prion-infected tissues were treated using different CAP-generating prototypes. Surfaces were then examined for the presence of residues using very sensitive fluorescence epi-microscopy. Prion residual infectivity was determined using the …

The Uncertainty And Psychological Health Of Family Caregivers Of Patients With Delirium In Intensive Care Units, Amal Shokri Haji Assa

Theses and Dissertations (ETD)

Each year, more than 5 million patients are admitted to an intensive care unit (ICU) in the United States, and up to 80 % of these patients develop delirium. Delirium is a common indicator of acute brain dysfunction in the ICU and a predictor of mortality, longer ICU/hospital stay, and long-term cognitive impairment. Family caregivers are a valuable resource in preventing, detecting, and managing delirium in the ICU. However, witnessing delirium episodes can generate adverse psychological symptoms in family caregivers that may compromise their health and well-being. Research in this area has demonstrated a gap in the literature regarding how …

Effect Of Botox And Therapy On Spasticity In Cerebral Palsy: A Critically Appraised Topic, Rachel Bray Mot/S, Tatum Cabot Mot/S, Peyton Clark Mot/S, Cameron Goodman Mot/S, Tarason Moore Mot/S, Claire Napier Mot/S

Master of Occupational Therapy Student Critically Appraised Topics

Children diagnosed with Cerebral Palsy often experience upper limb spasticity. Research has shown Botox injections in combination with occupational therapy can reduce the effects of spasticity in the upper limb. This literature review aims to determine how long is the appropriate duration of occupational therapy to administer after Botox injections to see decreased spasticity in the upper limbs.

The Development Of A Brain Penetrating Erythropoietin For The Treatment Of Alzheimer’S Disease, Joshua Yang

KGI Theses and Dissertations

The development of a neurotherapeutic for the treatment of Alzheimer’s Disease (AD) is challenging due to limited endpoint efficacy. Erythropoietin (EPO), a hematopoietic neurotrophin, is a potential therapeutic for AD but has limited blood-brain barrier (BBB) permeability. A chimeric fusion protein of EPO bound to the transferrin receptor monoclonal antibody (cTfRMAb) can act as a molecular trojan horse for brain drug delivery, shuttling EPO into the brain via the transvascular route. However, cTfRMAbs have Fc-effector function adverse effects, and removal of the Fc N-linked glycosylation site by substituting Asn with Gly (cTfRMAb-N292G-EPO) reduces this Fc effector function. Hence, developing this …

A Puzzling Case Of Normal Pressure Hydrocephalus In The Outpatient Setting, Shadi Shams, Asim Shafique, Marym Khan, James Bailey

Rowan-Virtua Research Day

Normal Pressure Hydrocephalus (NPH) is a disease of adulthood characterized by the triad of gait disturbance, dementia, and urinary incontinence. Since NPH shares a lot of characteristics with other disorders including neurodegenerative disorders and degenerative-dystrophic spine, it is usually underdiagnosed and undertreated. Combination of ventriculomegaly seen on a computerized tomography (CT) scan or magnetic resonance imaging (MRI) with clinical findings could be used in diagnosis of NPH. However, improvement of symptoms post spinal tap procedure would be a better indication of diagnosis. Currently, shunt placement is the best available modality of treatment for NPH. Here we present a case of …

Exploring The Viability Of A Microglia Attenuating Treatment Model For Fibromyalgia Patients, Rohan Yarlagadda

Rowan-Virtua Research Day

Fibromyalgia refers to a rheumatic condition experienced as pain all over the body without a specific cause. This is considered a diagnosis of exclusion. This classification seems to suggest that any treatment options for it are purely symptomatic and are not disease targeted. Its complex diagnosis and underlying pathology contribute to the challenge of medically addressing fibromyalgia. Without a strict cause, fibromyalgia is often treated symptomatically with CBT and SNRIs. However, recent research suggests that existing therapeutic approaches are not very effective, especially when considering long term benefits for this chronic condition. This beckons for novel treatment options for these …

Bells Palsy: A Late Complication Of Sars-Cov-2 Infection, Rohan Umrani, Sameer Akhtar, Sean Coulson, Brian Thomas, Yvette Wang

Rowan-Virtua Research Day

A 60 year old male with a PMH of SARS-CoV-2, OSA and primary hypogonadism presented with a chief complaint of left sided facial numbness and weakness.

Bells Palsy is commonly caused by HSV, VZV, Lyme disease and less commonly ischemia or local compression. It presents with facial paralysis and loss of taste in anterior 2/3 of tongue.

In the absence of definitive Lyme serologies despite history of tick bite, it is likely that this patient had Bell’s Palsy as a late manifestation of COVID-19.

Distinguishing Multiple System Atrophy Vs Parkinson’S Disease In An African American Woman, Mahoua Kane, Rebecca Smith, Venkat Venkataraman

Rowan-Virtua Research Day

An 87-year-old African American woman with a past medical history of atrial fibrillation on warfarin and peripheral neuropathy with a family history of myasthenia gravis presented to the Emergency Department. The primary reason was loss of consciousness upon standing. The patient was given the diagnosis of hypertension, cervical spinal stenosis, and Parkinson’s Disease. There is little improvement with medications for any of these conditions. Currently, patient has episodes of worsening BP, blackouts, dysphagia, snoring, decreasing voice pitch with trismus. In addition, the patient is positive for dizziness, mild resting tremor in left hand with rigidity, constipation, multiple UTIs and postural …

“Translation Of Hdac6 Pet Imaging Using [18f]Ekz-001 – Cgmp Production And Measurement Of Hdac6 Target Occupancy In Nhps” – A Review, Dania Rahal

Chemistry & Biochemistry Undergraduate Honors Theses

The inhibition of histone deacetylase 6 (HDAC6) has been reported to alleviate the effects of neurodegenerative diseases such as Alzheimer’s disease. The brain-penetrant PET radioligand [¹⁸F]EKZ-001 has high affinity and selectivity towards HDAC6 and therefore suggests great promise in therapeutic treatment studies and development for neurodegenerative diseases. “Translation of HDAC6 PET imaging using [¹⁸F]EKZ-001 – cGMP production and measurement of HDAC6 target occupancy in NHPs” has achieved an effective, fully automated method of producing [¹⁸F]EKZ-001 in compliance with current good manufacturing practices (cGMP) to support the translation of [¹⁸F]EKZ-001 PET for …

Dexmedetomidine Vs. Propofol In Postoperative Delirium Prevention, Jaclyn Burnett Rn, Srna, Montana Betts Rn, Srna, Christhian De Ochoa Rn, Srna, Maciej Chec Rn, Srna, Dwayne Accardo Dnp, Crna, Aprn

Doctor of Nursing Practice Projects

Purpose/Background Postoperative delirium (POD) is an acute neurological condition affecting large numbers of surgical patients in various practice settings. Patients suffering from this condition face postoperative complications, increased lengths of stay, and tremendous financial burden. Understanding the contributing factors for POD, and how adjustments in intraoperative agents can prevent or reduce the incidence, is a crucial aspect of anesthesia practice. This scoping review will examine associations between POD and the intraoperative use of propofol versus dexmedetomidine with general anesthesia.

Methods Studies in this review were limited to peer-reviewed literature, published in medical and nursing journals within the last five years. …

Immunomodulatory Roles Of The Lysosomal Sialidase Neuraminidase 1, Leigh Ellen Fremuth

Theses and Dissertations (ETD)

Background Sialic acids are key sugar moieties located at the non-reducing terminals of glycan chains on glycoproteins and glycolipids. By virtue of their location, they influence the functions and biochemical properties of the macromolecules they are bound to. Removal of sialic acids in mammalian cells is carried out by four sialidases, which are differentially expressed and localized in distinct subcellular compartments. Neuraminidase 1 (NEU1), the most abundant and ubiquitous of the four sialidases, functions primarily in the acidic environment of the lysosomes, but can hydrolyze substrates at the plasma membrane, at least in certain cell types. The enzyme initiates the …

Succinic Semialdehyde Dehydrogenase Deficiency (Ssadhd): Qualitative Needs Assessment For Patients With A Rare Neurological Disorder, Cassandra Bovee, Kayla Woodring

Annual Research Symposium

No abstract provided.

Current And Novel Neuroregenerative Therapies, Arrin Brooks

Theses, Dissertations and Capstones

Underlying the physical and cognitive deficits consequent of many neuropathologies is one common factor, the loss of neurons. While neurodegenerative diseases, stroke, and traumatic brain injury arise from a variety of etiologies, they all ultimately result in injury and/or death of neuronal cells and concomitant functional deficits. In the present work we primarily focus on current and potential treatments for localized lesions, particularly those in the striatum of Parkinson’s disease (PD) or the cortex as in stroke. First, we discuss a new surgical technique for deep brain stimulator (DBS) placement, as DBS is a mainstay treatment for movement disorders including …

Contrast-Induced Encephalopathy Following Diagnostic Coronary Angiography, Hytham Rashid, Andrew Good, Jonathan Brown, Tusharkumar Pansuriya, Alan Fisher Covin, Mir Ali Sadat

Gulf Coast Division GME Research Day 2022

No abstract provided.

Biologic Tnf-Α Inhibitors Reduce Microgliosis, Neuronal Loss, And Tau Phosphorylation In A Transgenic Mouse Model Of Tauopathy, Weijun Ou, Joshua Yang, Juste Simanauskaite, Matthew Choi, Demi M. Castellanos, Rudy Chang, Jiahong Sun, Nataraj Jagadeesan, Karen D. Parfitt, David H. Cribbs, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background

Tumor necrosis factor-α (TNF-α) plays a central role in Alzheimer’s disease (AD) pathology, making biologic TNF-α inhibitors (TNFIs), including etanercept, viable therapeutics for AD. The protective effects of biologic TNFIs on AD hallmark pathology (Aβ deposition and tau pathology) have been demonstrated. However, the effects of biologic TNFIs on Aβ-independent tau pathology have not been reported. Existing biologic TNFIs do not cross the blood–brain barrier (BBB), therefore we engineered a BBB-penetrating biologic TNFI by fusing the extracellular domain of the type-II human TNF-α receptor (TNFR) to a transferrin receptor antibody (TfRMAb) that ferries the TNFR into the brain via …

Developing Deep-Learning Methods For Diagnosis And Prognosis Of Pediatric Progressive Diseases Using Modern Imaging Techniques, Mahdieh Shabanian

Theses and Dissertations (ETD)

Purpose and Rationale. Central nervous system manifestations form a significant burden of disease in young children. There have been efforts to correlate the neurological disease state in tuberous sclerosis complex (TSC) neurological disease state with imaging findings is a standard part of patient care. However, such analysis of neuroimaging is time- and labor-intensive. Automated approaches to these tasks are needed to improve speed, accuracy, and availability. Automated medical image analysis tools based on 3D/2D deep learning algorithms can help improve the quality and consistency of image diagnosis and interpretation for cognitive disorders in infants. We propose to automate neuroimaging analysis …

The Concentration Of Brain Homogenates With The Amicon Ultra Centrifugal Filters, Joshua Yang, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Accurately measuring the brain concentration of a neurotherapeutic is critical in determining its pharmacokinetic profile in vivo. Biologics are potential therapeutics for neurologic diseases and biologics fused to an antibody targeting a transcytosis receptor at the Blood-Brain Barrier, designated as antibody-biologic fusion proteins, are Blood-Brain Barrier penetrating neurotherapeutics. The use of sandwich immunosorbent assays to measure concentrations of antibody-biologic fusion proteins in brain homogenates has become increasingly popular. The raw brain homogenate contains many proteins and other macromolecules that can cause a matrix effect, potentially interfering with the limit of detection of such assays and reduce the overall sample …

Multiple Sclerosis And Its Symptom Management Through Supplementation And Dietary Planning, Lindsey J. Davis

Selected Honors Theses

Multiple Sclerosis (MS) is an autoimmune, neuroinflammatory disorder that is characterized by the breakdown of myelinated axons in the Central and Peripheral Nervous Systems. It is a potentially debilitating autoimmune disease that affects almost 1 million people in the United States, and nearly 2.5 million people worldwide. The precise etiology of MS is still being researched, but much progress has been made towards understanding the molecular mechanisms and impactful ways to treat this disease. While there is still no cure, new treatment plans are constantly being orchestrated in effort to alleviate the burden that MS carries. Combination treatment plans have …

Does Subthalamic Deep Brain Stimulation Impact Asymmetry And Dyscoordination Of Gait In Parkinson’S Disease?, Deepak K. Ravi, Christian R. Baumann, Elena Bernasconi, Michelle Gwerder, Niklas K. Ignasiak, Mechtild Uhl, Lennart Stieglitz, William R. Taylor, Navrag B. Singh

Physical Therapy Faculty Articles and Research

Background. Subthalamic deep brain stimulation (STN-DBS) is an effective treatment for selected Parkinson’s disease (PD) patients. Gait characteristics are often altered after surgery, but quantitative therapeutic effects are poorly described. Objective. The goal of this study was to systematically investigate modifications in asymmetry and dyscoordination of gait 6 months postoperatively in patients with PD and compare the outcomes with preoperative baseline and to asymptomatic controls without PD. Methods. A convenience sample of thirty-two patients with PD (19 with postural instability and gait disorder (PIGD) type and 13 with tremor dominant disease) and 51 asymptomatic controls participated. Parkinson patients …

Insights Into The Mechanisms Of Brain Endothelial Erythrophagocytosis, Jiahong Sun, Prema Vyas, Samar Mann, Annlia Paganini-Hill, Ane C. F. Nunes, Wei Ling Lau, David H. Cribbs, Mark J. Fisher, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

The endothelial cells which form the inner cellular lining of the vasculature can act as non-professional phagocytes to ingest and remove emboli and aged/injured red blood cells (RBCs) from circulation. We previously demonstrated an erythrophagocytic phenotype of the brain endothelium for oxidatively stressed RBCs with subsequent migration of iron-rich RBCs and RBC degradation products across the brain endothelium in vivo and in vitro, in the absence of brain endothelium disruption. However, the mechanisms contributing to brain endothelial erythrophagocytosis are not well defined, and herein we elucidate the cellular mechanisms underlying brain endothelial erythrophagocytosis. Murine brain microvascular endothelial cells (bEnd.3 …

Machine Learning Classification Of Traumatic Brain Injury Patients Versus Healthy Controls Using Arterial Spin Labeled Perfusion Mri, Vanessa I. Grass

Dissertations, Theses, and Capstone Projects

Traumatic brain injury (TBI) is one of the most common causes of death and disability worldwide, yet accurate in vivo detection of TBI neuropathology remains challenging due to complexities in the structural and functional changes observed post-injury as well as limitations in conventional neuroimaging modalities. Although advanced neuroimaging techniques such as arterial spin labeling (ASL) can noninvasively assess cerebral blood flow (CBF) changes observed post-injury, this technique is underutilized in TBI research partly due to the low signal-to-noise-ratio (SNR) inherent in ASL imaging. The aim of the current study is to examine the use of machine learning, specifically a Support …

Posterior Reversible Encephalopathy Syndrome (Pres), Brittany Fera, Andrew Caravello

Rowan-Virtua Research Day

Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiographic syndrome that describes certain neuroimaging findings in association with clinical symptoms such as headache, seizure, encephalopathy and vision changes. Classically, PRES is associated with poorly controlled hypertension, and patients present with elevated blood pressure in addition to their symptoms. Most importantly, imaging findings and symptoms are typically reversible, and are a separate entity from ischemic or hemorrhagic cerebrovascular accidents or autoimmune causes of similar symptoms, such as multiple sclerosis.

Syncope Or Seizure?, Joseph Heron, Kevin Dwyer

Rowan-Virtua Research Day

Syncope is a common complaint in the emergency departments, accounting for 1-2% of visits, and can approach admission rates of a staggering 85%. The causes and conditions can be numerous, ranging from benign to life threatening. A good background history can go a long way in determining the etiology of the patient’s syncope. We describe a case of an elderly male who presented with a reported chief complaint of seizures, another syncope-mimic seen in the emergency department. He had a history of CAD, HTN, AAA, and osteoarthritis but no prior history of cardiac arrhythmia, MI, or structural heart disease. The …

Spontaneous Conus Medullary Infarction In The Absence Of Cardiovascular Risk Factors, Bavica Gummadi, Jaffer Ahmed, Swarna Rajagopalan

Rowan-Virtua Research Day

Spinal cord infarction (SCI) is rare and most often occurs in individuals with predisposing cardiovascular risk factors and traumatic injuries

As there are no distinct diagnostic criteria for SCI, diagnosis is difficult in patients presenting without predisposing factors and is often mistaken for transverse myelitis.

Delay in early diagnosis contributes to the high case fatality rate of SCI.

This case highlights the importance of including SCI in the differential of a patient with acute paraparesis even in the absence of co-existing risk factors.

Meralgia Paresthetica As A Complication Of Laparoscopic Cholecystectomy In A Post Partum Teenager, Puthenmadam Radhakrishnan, Wajihah Memon, Prasanna Tati

Rowan-Virtua Research Day

An 18 year old G1P1 female, 3 months postpartum presented to the emergency department with abdominal pain that was diagnosed as cholelithiasis and choledocholithiasis. Following a cholecystectomy surgery, the patient developed weakness and gait abnormality that was diagnosed as neuralgia.

Meralgia paresthetica is such an understudied diagnosis that its incidence is unknown. Patients who are 30-85 years old, obese, diabetic, and/or pregnant are at an increased risk for the condition. This case calls attention to the underdiagnosis of meralgia paresthetica in pediatric patients with comorbidities. As aforementioned risk factors increase in the pediatric population due to societal and environmental factors, …

From Left Arm Numbness To Incidental Pituitary Macroadenoma, Melissa Itidiare Locke

Rowan-Virtua Research Day

Pituitary adenomas are the most common tumors in the sella turcica. The symptoms of vision loss or change is due to the anatomical location of the pituitary tumor beneath the optic nerve. (2) As the tumor grows in size it can compress the optic nerve and vision changes will occur. Our case demonstrates a 40 year old male who had one brief 1 time episode of blurry vison and dull intermittent headaches that was not debilitating in nature. A discovery of pituitary adenoma prior to onset of symptoms of constant vision changes or elevated hormones are crucial to a more …

A Novel Case Of Hhv-6 Meningoencephalitis In An Immunocompetent Adult, Justin Berkner, Kishan Patel

Rowan-Virtua Research Day

We present a case of a 56-year-old female who presented with HHV6 encephalitis. She initially presented with altered mental status. Our patient ultimately made a full recovery several days later with only some mild intermittent episodes of confusion. Currently there are no other case reports of HHV6 encephalitis in the adult population.

Initial Multiple Sclerosis Diagnosis In The Emergency Department, Adam Kandil, James Espinosa, Henry Schuitema

Rowan-Virtua Research Day

Multiple sclerosis is a chronic autoimmune disease consisting of inflammation, demyelination and loss of axon integrity in the central nervous system. Like many autoimmune diseases, its severity, initial presentation and symptomatology vary. MS is typically onset in young adults between twenty to forty years old, and has been found two-three times more likely in women than in men. As a chronic illness, like many others, it can present in the emergency department as an undifferentiated neurologic complaint. This is a case report of new onset multiple sclerosis in the emergency department, outlining the importance of a broad set of differential …