Nervous System Diseases Commons^™

A Potential Role For Substance P In West Nile Virus Neuropathogenesis, Shannon E Ronca, Sarah M Gunter, Rebecca Berry Kairis, Allison Lino, Jonathan Romero, Robia G Pautler, Alan Nimmo, Kristy O Murray

Faculty, Staff and Students Publications

Of individuals who develop West Nile neuroinvasive disease (WNND), ~10% will die and >40% will develop long-term complications. Current treatment recommendations solely focus on supportive care; therefore, we urgently need to identify novel and effective therapeutic options. We observed a correlation between substance P (SP), a key player in neuroinflammation, and its receptor Neurokinin-1 (NK1R). Our study in a wild-type BL6 mouse model found that SP is upregulated in the brain during infection, which correlated with neuroinvasion and damage to the blood−brain barrier. Blocking the SP/NK1R interaction beginning at disease onset modestly improved survival and prolonged time to death in …

Comprehensive Care To Improve Quality Of Life: A Case Of Childhood Adrenoleukodystrophy, Miraal S. Dharamsi, Adrian A. Mejia, Cecilia De Vargas

HCA Healthcare Journal of Medicine

The childhood cerebral form of adrenoleukodystrophy (ALD) causes rapid demyelination of cerebral white matter and is clinically characterized by hyperactivity, emotional changes, and poor school performance, as well as progressive cognitive, visual, auditory, speech, and motor decline. While aggressive behavior is a known complication of ALD, treatment of the disease is limited. Moreover, behavioral management is not well described in the available literature, particularly from a psychiatric standpoint. In this case presentation, the patient’s parents reported significant agitation and aggression, which may have been secondary to verbal deficits, in addition to the general neuropathological implications of this disease. Although this …

Multicomponent Approach To Delirium Prevention In The Acute Care Setting: An Evidence-Based Quality Improvement Project., Kelley James

Doctor of Nursing Practice Papers

Background: Acutely ill, hospitalized individuals are at an increased likelihood of developing delirium. Between 30-35% of those patients admitted to the hospital will develop delirium, and as a result, these individuals will face an increased risk of mortality, adverse medical events, restraint usage, and incur a more extended hospitalization. The literature supports early screening utilizing the Confusion Assessment Method (CAM) tool and nurse-driven, multicomponent interventions to aid in preventing its development.

Environment: This project was implemented in a long-term, acute care facility specializing in patients requiring long-term mechanical ventilation, advanced wound care, pulmonary and respiratory care, and the rehabilitation of …

Development Of Graphical Models And Statistical Physics Motivated Approaches To Genomic Investigations, Yashwanth Lagisetty

Dissertations and Theses (Open Access)

Identifying genes involved in disease pathology has been a goal of genomic research since the early days of the field. However, as technology improves and the body of research grows, we are faced with more questions than answers. Among these is the pressing matter of our incomplete understanding of the genetic underpinnings of complex diseases. Many hypotheses offer explanations as to why direct and independent analyses of variants, as done in genome-wide association studies (GWAS), may not fully elucidate disease genetics. These range from pointing out flaws in statistical testing to invoking the complex dynamics of epigenetic processes. In the …

Myasthenia Gravis, Rebecca Wheeler

Nursing Student Class Projects (Formerly MSN)

Myasthenia gravis (MG), a neuromuscular and autoimmune disorder, is not completely understood by clinicians and scientists. The primary cause is thought to be anti-Acetylcholine receptor antibodies that attack the neuromuscular junction, causing destruction of post-synaptic junctional folds and blockade of the receptor. This causes frequent weakness and fatigability of voluntary muscles, making activities of daily living difficult for those living with MG. Although it is not an incredibly prevalent disease, the incidence is increasing in the United States due to better testing and diagnosis. Treatments are available, including cholinesterase inhibitors that raise the concentration of Acetylcholine at the neuromuscular junction …

A Rare Presentation Of Pituitary Macroadenoma, Saumya Mittal

Manipal Journal of Medical Sciences

A 37 year old lady presented to the hospital with severe headache. The lady had prior episodes of headache that lasted for 1 to 2 days and was associated with nausea, vomiting, photophobia and phonophobia. She was on treatment for episodic migraine. However, this time she had a severe and worse headache which was not improving on her regular medications. She had associated diplopia that she noted initially and had ptosis at the time of presentation to the hospital as well. Lady had ptosis with medial rectus palsy, with normal size normal reaction of pupil. There was mild frontal sinus …

Meta-Analysis Of 175 Patients With Covid-19 And Seizures, Status Epilepticus, Or Cortical Myoclonus: An Individual Patient Data Analysis, Aditi Kappagantu Bs, Helena A. Brantz Ms, Amman Bhasin Ba, Cristina Jageka Bs, Rooqash Ali Md, Izzy Saef Md, Brittany M. Stopa Mph, Ayaz Khawaja Md

Medical Student Research Symposium

Objective

To characterize management and outcomes of seizures, status epilepticus, and cortical myoclonus in COVID-19, with individual patient data analysis of published literature.

Methods

Systematic literature review was conducted in accordance with PRISMA guidelines. Criteria included new-onset seizures, status epilepticus, and/or cortical myoclonus with concomitant COVID-19. COVID-19 severity was dichotomized into mild and severe cases. Good outcome was defined as discharge without severe deficits, and/or return to baseline.

Results

A total of 105 studies reporting 176 patients (male 56.3%;mean age 47.8,SD 25.6) were included. Status epilepticus occurred in 47 patients (26.7%) and myoclonus in 41 (23.3%). Severe COVID-19 occurred in …

Potential Impact Of 2017 American College Of Cardiology/American Heart Association Hypertension Guideline On Contemporary Practice: A Cross-Sectional Analysis From Ncdr Pinnacle Registry, Aliza Hussain, Salim S. Virani, Luke Zheng, Ty J. Gluckman, William B. Borden, Frederick A. Masoudi, Thomas M. Maddox

Office of the Provost

Background Clinical implications of change in the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on the diagnosis and management of hypertension, compared with recommendations by 2014 expert panel and Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7), are not known. Methods and Results Using data from the NCDR (National Cardiovascular Data Registry) PINNACLE (Practice Innovation and Clinical Excellence) Registry (January 2013-Decemver 2016), we compared the proportion and clinical characteristics of patients seen in cardiology practices diagnosed with hypertension, recommended antihypertensive treatment, and achieving blood pressure (BP) goals …

Identification Of Therapeutic Targets For Th17 Cell-Mediated Diseases, Jin Wang

Theses and Dissertations (ETD)

Hypersensitivity and autoimmune diseases are complex synergistic effect of environmental, genetic and other factors. T helper 17 (Th17) cells play a critical role in the immune pathology. Th17 cells are a group of specialized CD4+ T cells with potential pro-inflammatory function which are different from other T cells such as T helper 1 (Th1) cells or T helper 2 (Th2) cells. Th17 cell development and differentiation processes are strictly regulated through complex pathways. Th17 cells are characterized by secreting cytokines such as IL-17 and IL-22. Studies have shown that Th17 cells and IL-17 have been implicated in the pathogenesis of …

Crel And Wnt5a/Frizzled 5 Receptor-Mediated Inflammatory Regulation Reveal Novel Neuroprotectin D1 Targets For Neuroprotection, Jorgelina M. Calandria, Khanh V. Do, Sayantani Kala-Bhattacharjee, Andre Obenaus, Ludmila Belayev, Nicolas G. Bazan

School of Medicine Faculty Publications

Abstract: Wnt5a triggers inflammatory responses and damage via NFkB/p65 in retinal pigment epithelial (RPE) cells undergoing uncompensated oxidative stress (UOS) and in experimental ischemic stroke. We found that Wnt5a-Clathrin-mediated uptake leads to NFkB/p65 activation and that Wnt5a is secreted in an exosome-independent fashion. We uncovered that docosahexaenoic acid (DHA) and its derivative, Neuroprotectin D1 (NPD1), upregulate c-Rel expression that, as a result, blunts Wnt5a abundance by competing with NFkB/p65 on the Wnt5a promoter A. Wnt5a increases in ischemic stroke penumbra and blood, while DHA reduces Wnt5a abundance with concomitant neuroprotection. Peptide inhibitor of Wnt5a binding, Box5, is also neuroprotective. DHA-decreased …

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.

Full- Versus Sub-Regional Quantification Of Amyloid-Beta Load On Mouse Brain Sections, Yuu Ohno, Riley Murphy, Matthew Choi, Weijun Ou, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Extracellular accumulation of amyloid-beta (Aβ) plaques is one of the major pathological hallmarks of Alzheimer's disease (AD), and is the target of the only FDA-approved disease-modifying treatment for AD. Accordingly, the use of transgenic mouse models that overexpress the amyloid precursor protein and thereby accumulate cerebral Aβ plaques are widely used to model human AD in mice. Therefore, immunoassays, including enzyme-linked immunosorbent assay (ELISA) and immunostaining, commonly measure the Aβ load in brain tissues derived from AD transgenic mice. Though the methods for Aβ detection and quantification have been well established and documented, the impact of the size of the …

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 Preliminary Investigation Of Neuroantibody Levels, Prevalence, And Environmental Factors In Patients With Neurological Dysfunction, Jihan Azar

Theses and Dissertations

Nervous system damage comprises a large proportion of diseases worldwide. It is also the most difficult to diagnose. Biomarkers for nervous system damage are needed in order to diagnose these diseases early enough to allow for intervention. In this study, we recruited patients from two Egyptian hospitals with MCI, ET and NMS and health references. Serum autoantibody levels against neural proteins and heavy metals were analyzed and compared. Immunoglobulin G (IgG) antibodies against neurofilament H (NFH), Glial Fibrillary Acidic Protein (GFAP), Myelin Basic Protein (MBP) and alpha synuclein (a-SYN) and Immunoglobulin M (IgM) antibody against neurofilament light (NFL) were among …

Characterization Of Retinal Function And Structure In The Mptp Murine Model Of Parkinson's Diseasecharacterization Of Retinal Function And Structure In The Mptp Murine Model Of Parkinson’S Disease, Katie K N Tran, Vickie H Y Wong, Jeremiah K H Lim, Ali Shahandeh, Anh Hoang, David I Finkelstein, Bang V Bui, Christine T O Nguyen

Faculty, Staff and Student Publications

In addition to well characterized motor symptoms, visual disturbances are increasingly recognized as an early manifestation in Parkinson's disease (PD). A better understanding of the mechanisms underlying these changes would facilitate the development of vision tests which can be used as preclinical biomarkers to support the development of novel therapeutics for PD. This study aims to characterize the retinal phenotype of a mouse model of dopaminergic dysfunction and to examine whether these changes are reversible with levodopa treatment. We use a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD to characterize the neurotoxic effects of MPTP on in vivo retinal function (electroretinography, …

Effects Of Music Exposure On Autobiographical Memory In Alzheimer's Patients: A Systematic Review And Meta-Analysis, Gregory Vance

Honors Theses

The progression of Alzheimer’s disease is primarily characterized by a loss of memory concerning past events, as well as a lack in ability to create new memories. While this spans across many subsets of memory, such as recognition, recall, and autobiographical memory, there seems to be a lesser impact on musical memory in those with Alzheimer’s. Multiple studies have suggested that exposure to music and introduction of music therapy can even improve other aspects of memory in Alzheimer’s patients. This systematic review and meta-analysis sought to examine the relationship between music exposure and autobiographical memory specifically. A pool of electronic …

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 …

Case Report: A Patient With Gait Dysfunction With Acute Inflammatory Demyelinating Polyneuropathy Masquerading As Diabetic Polyneuropathy, David Parkes, Russell Mordecai

Rowan-Virtua Research Day

New onset gait dysfunction often prompts admission to the hospital for further evaluation. The typical patient is an elderly person who normally is self-sufficient but had recently experienced a decline in their ability to care for themselves. Sometimes, however, those who present with gait dysfunction do not fit the expected demographic. These individuals raise concern for less common “zebra” presentations of neurological dysfunction. We describe one such rare case of a 39-year-old female with a new onset of type 2 diabetes mellitus and recent COVID-19 infection that presented to the emergency department with a sensation of bilateral lower extremity burning …

Impact Forces And Patterns Of Axonal Injury Differ Between Two Models Of Tbi, Edward Lai, David M Devilbiss

Rowan-Virtua Research Day

Traumatic brain injury (TBI) affects approximately 3.8 million Americans a year and results in complex neuropathological and neurocognitive sequelae. Animal models of TBI attempt to replicate the impact forces and pathology of injury in humans. However, in these models, the forces generated at the time of impact are poorly understood. Nonetheless, a variety of shear and strain forces generated at the time of impact can produce diffuse axonal injury. Injury to axons and neurons across a variety of brain regions resulting from axonal injury underlies the cognitive and behavioral impairments observed after TBI. Three critical brain regions, the corpus callosum …

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 …

A Case Of Intracranial Empyema After Bacterial Sinusitis, Eric Doane, Bhumi Shah, Robert Belfer

Rowan-Virtua Research Day

Acute sinusitis in the pediatric population is a common presentation in the emergency department. Most cases are viral and can be managed conservatively and will resolve spontaneously in 7-10 days. Even in cases of bacterial sinusitis, patients can typically be discharged with oral antibiotics and close follow up with the pediatrician.

There is however a small subset of patients who will develop a rare lethal complication, an intracranial empyema. While the incidence in the developed world has decreased as antibiotics become more available, it is still estimated to occur in up to 5% of severe cases requiring hospitalization (1) . …

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.

The Brodmann Area 39/40 Of The Brain In Alzheimer’S, Mild Cognitive Impairment, And No Cognitive Impairment Subjects At Advanced Age Demonstrate Comparable Levels Of Blood-Brain Barrier Breach, Dhara Rana, Forum Mangrola, Randel L. Swanson, Venkat Venkataraman, David A. Bennett, Zoe Arvanitakis, David Libon, Robert Nagele, Nimish Acharya

Rowan-Virtua Research Day

• Alzheimer’s disease (AD) is one of the most common form of dementia

• Mild cognitive impairment (MCI), specifically amnestic subtype, more likely to progress to AD

• Pathogenesis Theories:

• o Accumulation of amyloid-beta peptides and neurofibrillary tangles containing hyperphosphorylated neuronal tau protein
• o Blood Brain Barrier (BBB) dysfunction is associated with AD pathogenesis

• Brodmann area 39/40: regions of parietal cortex are responsible for language, spatial cognition, memory retrieval, attention, phonological processing, and emotional processing

• Hypothesis: An increased BBB permeability in Brodmann area 39/40 of AD and age-matched MCI and no cognitive impairment (NCI) subjects

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 …

Cyclin C Is Sufficient For Myoblast Differentiation-Induced Mitochondrial Fragmentation, Alicia N. Campbell, Randy Strich

Rowan-Virtua Research Day

One of the largest and most dynamic tissues in the body, skeletal muscle, requires constant regeneration and upkeep. Dysregulation of this regeneration process has been implicated in many neuromuscular diseases and myotonic dystrophies. Regeneration requires the differentiation of myogenic lineages including exiting the cell cycle, gene expression changes, and fusing of myoblasts into multinucleate myotubes. Part of this reconstruction requires the breakdown and repopulation of mitochondrial networks. At the early onset of myoblast differentiation, there is an upregulation of dynamin-related protein, Drp1, and an increase in mitophagy mediated by sequestosome (SQSTM1) removal of mitochondria.

Previously, our lab has shown that …

Charles Bonnet Syndrome: A Case Report, Christian Scouarnec, Martin M. Forsberg

Rowan-Virtua Research Day

Charles Bonnet syndrome (CBS) involves nonthreatening hallucinations in patients who have no neurological and no psychological abnormalities but with significant visual impairment secondary to ocular disease, such as macular degeneration, cataracts and diabetic retinopathy. When a patient loses vision, their visual system doesn’t process new images. Without data coming through the eyes, the brain fills the void and makes up images or recalls stored images for you to see and this is what causes the hallucinations in CBS.

Many physicians are unaware of CBS and its prevalence, and with proper detection, physicians can help treat their patients with a frequently …

Substrate-Specific Effect On Sirtuin Conformation And Oligomerization, Jie Yang, Shannon L. Dwyer, Nathan I. Nicely, Brian P. Weiser

Rowan-Virtua Research Day

Human sirtuins are a family of nicotinamide adenine dinucleotide (NAD +)-dependent enzymes that are responsible for removing acyl modifications from lysine residues. Sirtuins are involved in the formation and proliferation of cancers and are thought to regulate the progression of neurodegenerative diseases. Although sirtuins can be pharmacologically targeted by small molecules, it is not easy to modulate the substrate selectivity of sirtuins despite the chemical diversity of their substrates. Here, we report substrate-specific effects on sirtuin conformation and oligomerization that regulate enzyme deacylase activity. We used fluorescent acyl peptide probes to study substrate interactions with two sirtuin isoforms: SIRT2 and …

Plasmalogen Deficiency: A Risk Factor For Dementias And Potential Treatment Target, Mitchel A. Kling, Mallika Mendu, Rima F. Kaddurah-Daouk, Sheldon Jordan, Dayan B. Goodenowe

Rowan-Virtua Research Day

Altered lipid metabolism is implicated in the risk of sporadic Alzheimer’s disease (AD) and related dementias (ADRD); however, the precise mechanisms accounting for findings from observational studies remains to be fully elucidated.

Plasmalogens are a subclass of integral membrane phospholipids with unique properties that appear to play important roles relevant to the pathophysiology of AD and ADRD, including vesicle fusion necessary for synaptic neurotransmitter release, modulation of membrane fluidity and microdomain dynamics, membrane antioxidant functions, and neuroprotection. Like the more familiar phosphatides, plasmalogens are synthesized on a 3-carbon glycerol backbone; however, they differ from phosphatides by the presence of a …

A Case Of Acute Disseminated Encephalomyelitis In An Adult Male With Bipolar Disorder, Jinisha Patwa, Tracey Harris

Rowan-Virtua Research Day

Acute disseminated encephalomyelitis (ADEM) is a rare demyelinating disease characterized by inflammation of the brain and spinal cord. The rapidly progressive inflammation in the central nervous system is known to occur in response to a prior infection or immunization.

The clinical signs of ADEM may manifest up to 60 days post illness or vaccination. Some develop encephalopathy and neurologic symptoms which include confusion, psychosis, and tetraparesis. Paresthesia of the limbs and muscular atrophy indicate a worse prognosis and higher risk of relapse as opposed to those with only CNS involvement. A predominantly psychiatric presentation is also possible.

Risk factors include …

Effect Of Osteopathic Manipulative Treatment In Patients With Postural Orthostatic Tachycardia Syndrome (Pots): A Literature Review, Sidharth Sahni, Harrison Jordan, Binoy Desai, Danielle Cooley, Alexander King

Rowan-Virtua Research Day

Postural Orthostatic Tachycardia Syndrome (POTS) is characterized by autonomic dysregulation resulting in diminished blood flow and excessive tachycardia.

POTS has been scarcely studied in the clinical setting. A review of literature generated only four articles, only one of which met the established criteria.

A follow up study to evaluate the effect of OMT on the quality of life for patients with POTS is planned. The hypothesis is that osteopathic manipulation plays a role in the management of POTS, as patients should experience improvement in their symptoms and their overall quality of life.