Nervous System Diseases Commons^™

Focal Cortical Dysplasia With Prolonged Ictal Asystole, A Case Report, Ahmad Wali, Fowzia Siddiqui

Section of Neurology

Introduction: Cortical dysplasia carries significant morbidities such as seizures and delayed milestones. Focal cortical dysplasia (FCD) causes refractory epilepsy with various seizure types depending on the location and extent of the dysplasia. FCD in the temporal region and the insular cortex may cause ictal bradycardia (IB) and ictal asystole (IA). Video EEG (VEEG) with simultaneous EKG recording can better diagnose these cardiac abnormalities in FCD. We describe a case of refractory epilepsy. The patient's clinical seizures were usually followed by syncope. VEEG revealed frequent seizures some of which were associated with prolonged ictal asystole.
Results: A 15 years old female …

Systems Genetics And Systems Biology Analysis Of Paraquat Effects In Bxd Recombinant Inbred Mice, Carolina Del Valle Torres Rojas

Theses and Dissertations (ETD)

Paraquat (PQ) is a chemical herbicide that is used in many countries including the United States. It is also highly acutely toxic to humans and has been used as a means of suicide. As PQ is applied mainly in agricultural settings, it moves to soil and well water. Chronic low dose exposure via drinking water may have adverse effects on humans, including increased risk for sporadic Parkinson’s disease (sPD). The etiology of sPD is unclear and the most accepted hypothesis states it is the result of the interaction between environmental factors and genetic susceptibility. Increasing evidence led us to infer …

Diagnosing And Managing Post-Stroke Aphasia, Shannon M. Sheppard, Rajani Sebastian

Communication Sciences and Disorders Faculty Articles and Research

Introduction: Aphasia is a debilitating language disorder and even mild forms of aphasia can negatively affect functional outcomes, mood, quality of life, social participation, and the ability to return to work. Language deficits after post-stroke aphasia are heterogeneous.

Areas covered: The first part of this manuscript reviews the traditional syndrome-based classification approach as well as recent advances in aphasia classification that incorporate automatic speech recognition for aphasia classification. The second part of this manuscript reviews the behavioral approaches to aphasia treatment and recent advances such as noninvasive brain stimulation techniques and pharmacotherapy options to augment the effectiveness of …

An Approach For The In-Vivo Characterization Of Brain And Heart Inflammation In Duchenne Muscular Dystrophy, Joanne Tang

Electronic Thesis and Dissertation Repository

Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by dystrophin loss—notably within muscles and CNS neurons. DMD presents as cognitive weakness, progressive skeletal and cardiac muscle degeneration until pre-mature death from cardiac or respiratory failure. Innovative therapies improved life expectancy, but this is accompanied by increased late-onset heart failure and emergent cognitive degeneration. Thus, there is an increasing need to both better understand and track disease pathophysiology in the dystrophic heart and brain prior to onset of severe degenerative symptoms. Chronic inflammation is strongly associated with skeletal and cardiac muscle degeneration, however chronic neuroinflammation’s role is largely unknown in …

Acute And Chronic Dosing Of A High-Affinity Rat/Mouse Chimeric Transferrin Receptor Antibody In Mice, Demi M. Castellanos, Jiahong Sun, Joshua Yang, Weijun Ou, Alexander C. Zambon, William M. Pardridge, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Non-invasive brain delivery of neurotherapeutics is challenging due to the blood-brain barrier. The revived interest in transferrin receptor antibodies (TfRMAbs) as brain drug-delivery vectors has revealed the effect of dosing regimen, valency, and affinity on brain uptake, TfR expression, and Fc-effector function side effects. These studies have primarily used monovalent TfRMAbs with a human constant region following acute intravenous dosing in mice. The effects of a high-affinity bivalent TfRMAb with a murine constant region, without a fusion partner, following extravascular dosing in mice are, however, not well characterized. Here we elucidate the plasma pharmacokinetics and safety of a high-affinity bivalent …

Effect Of S100b Deletion On Membrane Properties And Localization Of Ncald And Hpca, Natasha Hesketh

Graduate School of Biomedical Sciences Theses and Dissertations

Calcium signaling is particularly important for neuronal function. Neurons utilize a wide range of calcium-binding proteins. Dysregulation of such proteins is linked to neurodegeneration. Neurocalcin delta (NCALD), hippocalcin (HPCA), and S100B are calcium sensors that are expressed in the hippocampus, a brain region essential to memory and severely damaged in Alzheimer’s disease (AD). Despite the potential importance of these proteins, we do not fully understand the physiological significance of their relationship. Because NCALD and HPCA are known to interact with S100B, we hypothesized that the loss of S100B affects NCALD and HPCA localization, and therefore electrical properties, of hippocampal neurons. …

Challenges Of Doing Alzheimer’S Research In Costa Rica And Some Possible Solutions, Felipe Mejias

International Programs

Alzheimer's disease is a public health priority which has been researched for many years in the hope of finding a cure soon. Costa Rica has made significant progress in many areas of research; however, the research carried out in the country on Alzheimer's disease is very scarce. The present poster presents the challenges of developing scientific Alzheimer’s research in Costa Rica by reviewing current scientific research on Alzheimer's in Costa Rica and by conducting interviews with Costa Rican professionals who have conducted Alzheimer's research. The lack of investigative training of doctors, the difficulties in accessing patient data, and the lack …

Targeting The Transferrin Receptor To Develop Erythropoietin For Alzheimer’S Disease, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

"Alzheimer’s disease (AD) is the sixth leading cause of death in the United States with approximately 5.8 million Americans currently living with AD. Due to the lack of a disease modifying treatment for AD and the aging baby boomer generation, this number is projected to grow to 13.8 million by 2050 (Gaugler et al., 2019). Amyloid-beta (Aβ) plaque accumulation, one of the major pathological hallmarks of AD, can begin > 20 years before clinical symptoms of AD. By the time AD is clinically diagnosed, neuronal loss and neuropathological lesions (Aβ plaques and tau tangles) have already occurred in many brain regions …

The Current Neuroscientific Understanding Of Alzheimer's Disease, Rachel A. Brandes

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Alzheimer’s disease is a degenerative neurological illness characterized by the deterioration of brain regions implicated in memory and cognitive function. While researchers have yet to find a cure or effective treatment, they have gained a better understanding of its pathology and development. Through years of neuroscience research, scientists have discovered much of what happens in the brain during Alzheimer’s disease onset and how this causes its symptoms; many hypotheses regarding this aspect of the illness involve temporal lobe atrophy, neurofibrillary tangles, and amyloid plaques. Although Alzheimer’s disease affects millions of people every day, it seems that most are unaware of …

Assessment Of Intrinsic Hand Neuromuscular Physiology, Philemon Tsang

Electronic Thesis and Dissertation Repository

Alterations to the peripheral nervous system and neuromuscular physiology may impact hand function in a typical or clinical population, such as individuals with ulnar neuropathy. The mechanisms that influence these positive and negative changes are still not well understood. The three studies within my thesis aim to validate the reliability of decomposition-based quantitative electromyography (DQEMG) measurements and explore the changes in intrinsic hand neuromuscular physiology in a typical aging population and individuals recovering from a surgical intervention for severe ulnar neuropathy.

The purpose of the first study was to determine the test-retest reliability of near-fibre (NF) jiggle, a measure of …

Anxiety In Alzheimer's Disease, Zachary Cooper

Senior Honors Theses

Researchers familiar with Alzheimer’s disease have often noted the presence of comorbid anxiety symptomatology. Likewise, the occurrence of anxiety before the development of Alzheimer’s disease has been prevalent enough to warrant attention. This review seeks to elaborate on the pathophysiology behind these two conditions, and to accentuate overlapping aspects that promote a causal relationship between these two pathologies on the macroscopic and cellular levels. Subsequent evidence will show that these pathologies are not independent of each other, and that cellular mechanisms of pathology hint at their interrelatedness. Areas requiring further research that would clarify the relationship between Clinical Anxiety and …

Management Of Childhood Migraine By Headache Specialist Versus Non-Headache Specialists, Kelly Valentini, Radhika Gutta, Gunjanpreet Kaur, Ahmad Farooqi, Lalitha Sivaswamy

Medical Student Research Symposium

This study aims to compare the management practices of a headache specialist with non-headache specialists in the treatment of pediatric migraine. The use of appropriate rescue medications and prophylactic agents, application of neuro-imaging, and short-term outcomes are compared in children treated by the two groups of physicians. A retrospective cohort study was conducted utilizing the electronic medical records of children 3-18 years of age with migraine, who were evaluated at a tertiary care children’s hospital from 2016-2018. Of the 849 patients that met the study criteria, 469 were classified as having chronic migraine or high-frequency episodic migraine and were followed …

Evidence That Brain-Reactive Autoantibodies Contribute To Chronic Neuronal Internalization Of Exogenous Amyloid-Β1-42 And Key Cell Surface Proteins During Alzheimer's Disease Pathogenesis, Eric L Goldwaser, Nimish K Acharya, Hao Wu, George A Godsey, Abhirup Sarkar, Cassandra A Demarshall, Mary C Kosciuk, Robert G Nagele

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Blood-brain barrier (BBB) permeability is a recognized early feature of Alzheimer's disease (AD). In the present study, we examined consequences of increased BBB permeability on the development of AD-related pathology by tracking selected leaked plasma components and their interactions with neurons in vivo and in vitro. Histological sections of cortical regions of postmortem AD brains were immunostained to determine the distribution of amyloid-β1-42 (Aβ42), cathepsin D, IgG, GluR2/3, and alpha7 nicotinic acetylcholine receptor (α7nAChR). Results revealed that chronic IgG binding to pyramidal neurons coincided with internalization of Aβ42, IgG, GluR2/3, and α7nAChR as well as lysosomal compartment expansion in these …

Epilepsy Risk Among Survivors Of Intensive Care Unit Hospitalization For Sepsis, Tresah C. Antaya, Britney N. Allen, Lucie Richard, Salimah Z. Shariff, Gustavo Saposnik, Jorge Burneo

Neuroepidemiology Research Unit Project Summaries

Research Summary: Key Findings

• 407 (0.28%) patients developed epilepsy within 2 years of their ICU discharge, 103 (25.3%) of whom were exposed to sepsis.
• Sepsis survivors were significantly more likely to develop epilepsy, relative to non-septic ICU survivors.
• Among sepsis survivors, epilepsy risk increased with age and was higher among those with chronic kidney disease.

Ectopic Pregnancy In A Woman With T9 Ais A Paraplegia Secondary To High-Grade Spinal Cord Pilocytic Astrocytoma, Elisabeth K. Acker

Graduate Medical Education (GME) Resident and Fellow Research Day Posters

Ectopic pregnancy in a woman with T9 AIS A (motor complete, sensory complete) paraplegia secondary to a high-grade spinal cord pilocytic astrocytoma

Background

In the United States, 20,000 women of childbearing age have a spinal cord injury (SCI). While SCI induces transient amenorrhea immediately after injury, women generally have normal reproductive function after SCI, and their fertility is unimpaired. Medications that commonly manage complications of SCI should be avoided or discontinued during pregnancy. Complications inherent to SCI, including urologic issues, are often exacerbated during pregnancy.

Methods

This is a case report on a female Veteran who initially presented to the …

Combination Of Investigational Cell-Based Therapy And Deep Brain Stimulation To Alter The Progression Of Parkinson’S Disease, Nader El Seblani

Theses and Dissertations--Pharmacy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the motor symptoms are caused by progressive loss of midbrain dopamine neurons. There is no current treatment that can slow or reverse PD. Our current “DBS-Plus” clinical trial (NCT02369003) features the implantation in vivo of autologous Schwann cells (SCs) derived from a patient’s sural nerve into the substantia nigra pars compacta (SNpc) in combination with Deep Brain Stimulation (DBS) therapy for treating patients with advanced PD.

The central hypothesis of our research is that transdifferentiated SCs within conditioned nerve tissue will deliver pro-regenerative factors to enhance the survival of …

Recovery From Visual Dysfunction Following Mild Traumatic Brain Injury Is Associated With Adaptive Reorganization Of Retinal Inputs To Lateral Geniculate Nucleus In The Mouse Model Utilizing Central Fluid Percussion Injury., Vishal C. Patel

Theses and Dissertations

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality nationwide. Prevalence of mild TBI (mTBI) vastly outnumbers more severe forms however the associated morbidity has only recently gained public attention. Visual dysfunction is a significant component of mTBI associated morbidity with recovery of function linked with improvement in global outcomes. Examination of sensory and motor pathways in other brain injury paradigms support that recovery is largely dependent on adaptive plasticity of remaining connections. Current examinations of visual function recovery following mTBI is limited to identifying evidence for recovery and objective evidence for adaptive plasticity is limited. Therefore, …

Exploring The Heteromeric Interface Of The 5-Ht2a-Mglu2 Receptor Complex, Mohamed Aarif Abdul Kareem

Theses and Dissertations

Schizophrenia is a serious mental disorder characteristic of several neurotransmitters including dopamine, serotonin, and glutamate being in imbalance. Early therapies focused solely on dopamine antagonism and second-generation antipsychotics focused on the dopamine and serotonin systems and their respective G protein coupled receptor (GPCR) proteins. Although debate for dimerization of certain classes of GPCR exist, the establishment of an mGlu2-5-HT_2A heterocomplex, which is implicated in schizophrenia is of interest. Previous studies have used a mutation-based approach to identify transmembrane domain 4 (TM4) as the domain responsible in mGlu2 for mediating heteromerization before narrowing down the individual amino acids responsible for …

The Comparative Efficacy Of Amantadine Vs. Lcig Therapy For The Treatment Of Levodopa-Induced Dyskinesia In Patients With Advanced Parkinson's Disease, Katelynn Timony

Capstone Showcase

Introduction: Though levodopa-carbidopa therapy remains the gold standard of Parkinson’s disease (PD) treatment to this day, patients often experience increased dyskinetic activity as a result of long-term treatment; known as levodopa-induced dyskinesia (LID); the mechanism of which is not completely understood. In this review, the efficacy of two adjunct treatments for LID are compared: 1) the concomitant administration of amantadine, an antiviral medication with antidyskinetic properties; and 2) a new form of levodopa administration in the form of an intestinal gel delivered straight via a device much like an insulin pump.

Methods: Two systematic literature searches of primary, peer-reviewed articles …

Rna Sequencing Of Human Peripheral Nerve In Response To Injury: Distinctive Analysis Of The Nerve Repair Pathways., Andrew S. Welleford, Jorge E. Quintero, Nader El Seblani, Eric Blalock, Sumedha Gunewardena, Steven M. Shapiro, Sean M. Riordan, Peter Huettl, Zain Guduru, John A. Stanford, Craig G. Van Horne, Greg A. Gerhardt

Manuscripts, Articles, Book Chapters and Other Papers

The development of regenerative therapies for central nervous system diseases can likely benefit from an understanding of the peripheral nervous system repair process, particularly in identifying potential gene pathways involved in human nerve repair. This study employed RNA sequencing (RNA-seq) technology to analyze the whole transcriptome profile of the human peripheral nerve in response to an injury. The distal sural nerve was exposed, completely transected, and a 1 to 2 cm section of nerve fascicles was collected for RNA-seq from six participants with Parkinson's disease, ranging in age between 53 and 70 yr. Two weeks after the initial injury, another …

Investigations Of A Low Carbohydrate Ketogenic Diet As A Possible Treatment For Malignant Brain Tumors, Elizabeth Anaya

Regis University Student Publications (comprehensive collection)

Cancer is now the leading cause of premature death in the U.S. and second worldwide. However, all cancers on average have seen a 20% increase in 5-year survival in the last 30 years. This is not true for brain cancers which have only seen a 1% increase. Brain cancer is extremely hard to treat, costing the most money out of any other cancer. Nevertheless, Otto Warburg’s investigation of cancer as a metabolic disease has led to a variety of new promising treatments. One of these treatments involves starving cancer cells by cutting off their access to glucose, a key component …

Modeling Genetic Risk Factor Of Alzheimer's Disease "Sorl1" Using Patient Specific Pluripotent Stem Cells, Kamonchanok Kongsri

Chulalongkorn University Theses and Dissertations (Chula ETD)

Alzheimer’s disease is the most common neurodegenerative; cause of dementia and trends to increase in elder society. There is still not cure. A new strategy development for treatment is needed. SORL1 is a major genetic risk factor associated with sporadic AD. It correlates with degrading amyloid beta (Aβ) by sorting to lysosome. SORL1 overexpression has been reported that reduce Aβ production. However, the molecular mechanism that regulate in neurons is still unclear. The purpose of this study is to generate an effective drug discovery platform for identifying molecules that can modulate SORL1 level in human neurons by using induced pluripotent …