Diseases Commons^™

High Levels Of Iron Supplementation Prevents Neural Tube Defects In The Fpn1(Ffe) Mouse Model., Bethany A Stokes, Julia A Sabatino, Irene E. Zohn

Pediatrics Faculty Publications

BACKGROUND: Periconception maternal nutrition and folate in particular are important factors influencing the incidence of neural tube defects (NTDs). Many but not all NTDs are prevented by folic acid supplementation and there is a pressing need for additional strategies to prevent these birth defects. Other micronutrients such as iron are potential candidates, yet a clear role for iron deficiency in contributing to NTDs is lacking. Our previous studies with the flatiron (ffe) mouse model of Ferroportin1 (Fpn1) deficiency suggest that iron is required for neural tube closure and forebrain development raising the possibility that iron supplementation could prevent NTDs.

METHODS: …

5-Hydroxymethylcytosine Localizes To Enhancer Elements And Is Associated With Survival In Glioblastoma Patients, Kevin C. Johnson, E. Andres Houseman, Jessica E. King, Katharine M. Von Herrmann, Camilo E. Fadu, Brock C. Christensen

Dartmouth Scholarship

Glioblastomas exhibit widespread molecular alterations including a highly distorted epigenome. Here, we resolve genome-wide 5-methylcytosine and 5-hydroxymethylcytosine in glioblastoma through parallel processing of DNA with bisulfite and oxidative bisulfite treatments. We apply a statistical algorithm to estimate 5-methylcytosine, 5-hydroxymethylcytosine and unmethylated proportions from methylation array data. We show that 5-hydroxymethylcytosine is depleted in glioblastoma compared with prefrontal cortex tissue. In addition, the genomic localization of 5-hydroxymethylcytosine in glioblastoma is associated with features of dynamic cell-identity regulation such as tissue-specific transcription and super-enhancers. Annotation of 5-hydroxymethylcytosine genomic distribution reveal significant associations with RNA regulatory processes, immune function, stem cell maintenance and …

Administration Of Electroconvulsive Therapy For Depression Associated With Deep Brain Stimulation In A Patient With Post-Traumatic Parkinson's Disease: A Case Study, Miles G. Cunningham, Golnaz Yadollahikhales, Gordana Vitaliano, Craig Van Horne

Neurosurgery Faculty Publications

Background: Deep brain stimulation (DBS) has been shown to be effective for parkinsonian symptoms poorly responsive to medications. DBS is typically well-tolerated, as are the maintenance battery changes. Here we describe an adverse event during a battery replacement procedure that caused rapid onset of severe depression.

Case Presentation: The patient is a 58-year-old woman who was in a serious motor vehicle accident and sustained a concussion with loss of consciousness. Within weeks of the accident she began developing parkinsonian symptoms that progressively worsened over the subsequent 10 years. Responding poorly to medications, she received DBS, which controlled her movement symptoms. …

An Unusual Case Of Escherichia Coli Meningitis And Bacteremia In An Elderly Woman Presenting With Intractable Low Back Pain, Andrea M. Lauffer, Mahmoud Shorman, Carl Mccomas

Marshall Journal of Medicine

Abstract

Introduction:

We report an unusual case of E. coli meningitis in an elderly woman who presented to the emergency room with a chief complaint of intractable low back pain.

Case Description:

A 67 year old woman presented to the emergency room for a chief complaint of intractable low back pain. After admission, the patient developed delirium. Blood cultures were drawn. Patient underwent a lumbar puncture which revealed purulent cerebrospinal fluid. Results of the cerebrospinal fluid and blood cultures revealed pan-sensitive E. coli.

Conclusion:

In the geriatric population, delayed presentation of meningitis can occur for various reasons. With the older …

Spinal Cord Injury And Autonomic Dysreflexia- A Case Report, Apurva Bhatt, Brit Moore, Talal Asif, Kristy E. Steigerwalt, Rebecca R. Pauly

Marshall Journal of Medicine

Autonomic dysreflexia (AD) is a life threatening condition affecting patients with spinal cord lesions T6 level and above. A 51 year old male with a history of paraplegia due to a C6 spinal cord injury (30 years prior) presented with recurrent debilitating episodic diaphoresis, hypertension, low body temperature, and bradycardia. Previous hospitalizations presumed sepsis from UTI to be the etiology, however on further evaluation his symptoms were consistent with undiagnosed AD. This article describes a unique case presentation and reviews AD in depth, including the etiology, pathophysiology and management.

A New Sv2a Ligand For Epilepsy, Michael A. Rogawski

Michael A. Rogawski

Kcnq2 Encephalopathy, John Millichap, Kristen Park, Tammy N. Tsuchida, Bruria Ben-Zeev, Lionel Carmant, On Behalf Of The Rikee Consortium

Neurology Faculty Publications

Objective: To advance the understanding of KCNQ2 encephalopathy genotype–phenotype relationships and to begin to assess the potential of selective KCNQ channel openers as targeted treatments.

Methods: We retrospectively studied 23 patients with KCNQ2 encephalopathy, including 11 treated with ezogabine (EZO). We analyzed the genotype–phenotype relationships in these and 70 previously described patients.

Results: The mean seizure onset age was 1.8 ± 1.6 (SD) days. Of the 20 EEGs obtained within a week of birth, 11 showed burst suppression. When new seizure types appeared in infancy (15 patients), the most common were epileptic spasms (n = 8). At last follow-up, seizures …

Hdqlife: Development And Assessment Of Health-Related Quality Of Life In Huntington Disease (Hd), N E Carlozzi, S G Schilling, J-S Lai, J S Paulsen, E A Hahn, J S Perlmutter, C A Ross, N R Downing, A L Kratz, M K Mccormack, M A Nance, K A Quaid, J C Stout, R C Gershon, R E Ready, J A Miner, S K Barton, S L Perlman, S M Rao, S Frank, I Shoulson, H Marin, M D Geschwind, P Dayalu, S M Goodnight, D Cella

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

PURPOSE: Huntington disease (HD) is a chronic, debilitating genetic disease that affects physical, emotional, cognitive, and social health. Existing patient-reported outcomes (PROs) of health-related quality of life (HRQOL) used in HD are neither comprehensive, nor do they adequately account for clinically meaningful changes in function. While new PROs examining HRQOL (i.e., Neuro-QoL-Quality of Life in Neurological Disorders and PROMIS-Patient-Reported Outcomes Measurement Information System) offer solutions to many of these shortcomings, they do not include HD-specific content, nor have they been validated in HD. HDQLIFE addresses this by validating 12 PROMIS/Neuro-QoL domains in individuals with HD and by using established PROMIS …

Role Of Diffusion Tensor Imaging In Prognostication And Treatment Monitoring In Niemann-Pick Disease Type C1, Meghann Lau, Ryan Lee, Robin Miyamoto, Eun Sol Jung, Nicole Farhat, Shoko Yoshida, Susumu Mori, Andrea L. Gropman, Eva Baker, Forbes Porter

Neurology Faculty Publications

Niemann-Pick Disease, type C1 (NPC1) is a rapidly progressive neurodegenerative disorder characterized by cholesterol sequestration within late endosomes and lysosomes, for which no reliable imaging marker exists for prognostication and management. Cerebellar volume deficits are found to correlate with disease severity and diffusion tensor imaging (DTI) of the corpus callosum and brainstem, which has shown that microstructural disorganization is associated with NPC1 severity. This study investigates the utility of cerebellar DTI in clinical severity assessment. We hypothesize that cerebellar volume, fractional anisotropy (FA) and mean diffusivity (MD) negatively correlate with NIH NPC neurological severity score (NNSS) and motor severity subscores. …

The Role Of Glutaminase And Extracellular Vesicles In Macrophages And Microglia, Beiqing Wu

Theses & Dissertations

Glutamate serves as a crucial excitatory neurotransmitter that is essential for the proper functioning of the brain. However, excess levels of glutamate are neurotoxic and contribute to the pathogenesis of various neurodegenerative diseases, inducing HIV-1 associated neurocognitive disorders (HAND). Glutaminase 1 (GLS1) is an important mitochondrial enzyme responsible for producing glutamate from glutamine. GLS1 is upregulated during HAND and released from mitochondria to cytosol and extracellular space. However, why and how GLS1 is released remains unknown. In chapter II, we demonstrated that extracellular vesicles (EVs) carry GLS1 as cargos from cytosol to extracellular space during HIV infection and innate immune …

A Hypothesis For Using Pathway Genetic Load Analysis For Understanding Complex Outcomes In Bilirubin Encephalopathy, Sean M. Riordan, Douglas C. Bittel, Jean-Baptist Lepichon, Silvia Gazzin, Claudio Tiribelli, Jon F. Watchko, Richard P. Wennberg, Steven Shapiro

Manuscripts, Articles, Book Chapters and Other Papers

© 2016 Riordan, Bittel, Le Pichon, Gazzin, Tiribelli, Watchko, Wennberg and Shapiro.

Genetic-based susceptibility to bilirubin neurotoxicity and chronic bilirubin encephalopathy (kernicterus) is still poorly understood. Neonatal jaundice affects 60-80% of newborns, and considerable effort goes into preventing this relatively benign condition from escalating into the development of kernicterus making the incidence of this potentially devastating condition very rare in more developed countries. The current understanding of the genetic background of kernicterus is largely comprised of mutations related to alterations of bilirubin production, elimination, or both. Less is known about mutations that may predispose or protect against CNS bilirubin neurotoxicity. …

Can Gait Signatures Provide Quantitative Measures For Aiding Clinical Decision-Making? A Systematic Meta-Analysis Of Gait Variability Behavior In Patients With Parkinson’S Disease, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

A disturbed, inconsistent walking pattern is a common feature of patients with Parkinson's disease (PwPD). Such extreme variability in both temporal and spatial parameters of gait has been associated with unstable walking and an elevated prevalence of falls. However, despite their ability to discretise healthy from pathological function, normative variability values for key gait parameters are still missing. Furthermore, an understanding of each parameter's response to pathology, as well as the inter-parameter relationships, has received little attention. The aim of this systematic literature review and meta-analysis was therefore to define threshold levels for pathological gait variability as well as to …

Revealing The Quality Of Movement: A Meta-Analysis Review To Quantify The Thresholds To Pathological Variability During Standing And Walking, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

Neuromotor processes are inherently noisy, which results in variability during movement and fluctu-ations in motor control. Although controversial, low levels of variability are traditionally considered healthy, while increased levels are thought to be pathological. This systematic review and meta-analysisof the literature investigates the thresholds between healthy and pathological task variability.

After examining 13,195 publications, 109 studies were included. Results from over 3000 healthy sub-jects and 2775 patients revealed an overall positive effect size of pathology on variability of 0.59 forwalking and 0.80 for sway. For the coefficient of variation of stride time (ST) and sway area (SA), upperthresholds of 2.6% …

Micellular Electrokinetic Chromatography For Studying Amyloid Beta Oligomer Membrane Affinity, Andrew Bryson

Biomedical Engineering Undergraduate Honors Theses

Amyloid Beta (Aβ) was the major focus of this study. It is a peptide that is present in the brain with a high tendency to self-aggregate. When this protein aggregates, it forms oligomers and protofibrils which in turn are deposited as senile plaques in the brain. The reason for the concern with these plaques is their association with the neurological disorder Alzheimer’s disease. It has been found that the most dangerous oligomers are formed in a portion of the plasma membrane known as lipid rafts. The purpose of this study was to understand how micelles affect the aggregation properties of …

Gene Expression Profiling In An Alzheimer's Disease Mouse Model, Matthew R. Dalton

Senior Honors Theses

Explaining precisely how Alzheimer’s disease (AD)—the world’s most common form of dementia—materializes in the human brain has proven to be one of the most elusive ends in modern medicine. Progressive memory loss, neurodegeneration, and the presence of abnormal protein aggregates of amyloid-beta (Aβ) and neurofibrillary tangles (NFT) characterize this disease. Genome sequencing provides researchers with the ability to better identify disease-related changes in gene expression, some of which may play a role in the initiation and progression toward the AD-like state. Intimate interactions between tissues have been observed in many diseases, particularly between the brain and blood. This analysis seeks …

Using A Tailored Health Information Technology- Driven Intervention To Improve Health Literacy And Medication Adherence In A Pakistani Population With Vascular Disease (Talking Rx) - Study Protocol For A Randomized Controlled Trial, Ayeesha Kamran Kamal, Abdul Muqeet, Kashfa Farhat, Wardah Khalid, Anum Jamil, Ambreen Gowani, Aliya Amin Muhammad, Fabiha Zaidi, Danyal Khan, Touseef Elahi, Shahrukh Sharif, Syedah Saira Bokhari, Nasir Rahman, Fateh Ali Tipoo Sultan, Saleem Sayani, Salim S. Virani

Section of Internal Medicine

Background: Vascular disease, manifesting as myocardial infarction and stroke, is a major cause of morbidity and mortality, especially in low- and middle-income countries. Current estimates are that only one in six patients have good adherence to medications and very few have sufficient health literacy. Our aim is to explore the effectiveness and acceptability of Prescription Interactive Voice Response (IVR) Talking Prescriptions (Talking Rx) and SMS reminders in increasing medication adherence and health literacy in Pakistani patients with vascular disease.
Methods: This is a randomized, controlled, single center trial. Adult participants, with access to a cell phone and a history of …

Neurocognitive Dysfunction In Brain Tumor Patients Following Radiation Therapy: A Review Of Biological Hypotheses, Current Treatment Outcomes, And Novel Therapeutic Strategies, Raj Singh

Marshall Journal of Medicine

Given the difficulty of surgical resection of brain neoplasms located adjacent to vital structures of the brain as well as the challenges posed by the blood-brain-barrier for the efficacy of chemotherapeutic agents, whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) are often turned to for patients with brain metastases as well as primary brain neoplasms. Though radiation therapy may be successful in local control of these tumors, many patients experience treatment-related neurocognitive issues later in life. In this review, we examine cognitive dysfunction in brain tumor patients following radiation therapy, with an emphasis on the pediatric population. Articles were …

Differential Rna Expression Profile Of Skeletal Muscle Induced By Experimental Autoimmune Myasthenia Gravis In Rats, Henry J. Kaminski, Keiichi Himuro, Jumana Alshaikh, Bendi Gong, Georgiama Cheng, Linda L. Kusner

Neurology Faculty Publications

The differential susceptibility of skeletal muscle by myasthenia gravis (MG) is not well understood. We utilized RNA expression profiling of extraocular muscle (EOM), diaphragm (DIA), and extensor digitorum (EDL) of rats with experimental autoimmune MG (EAMG) to evaluate the hypothesis that muscles respond differentially to injury produced by EAMG. EAMG was induced in female Lewis rats by immunization with acetylcholine receptor purified from the electric organ of the Torpedo. Six weeks later after rats had developed weakness and serum antibodies directed against the AChR, animals underwent euthanasia and RNA profiling performed on DIA, EDL, and EOM. Profiling results were validated …

Spatial And Temporal Homogeneity Of Driver Mutations In Diffuse Intrinsic Pontine Glioma., Hamid Nikbakht, Eshini Panditharatna, Leonie G Mikael, Rui Li, Tenzin Gayden, Alan Siu, Javad Nazarian, + 17 More

Neurological Surgery Faculty Publications

Diffuse Intrinsic Pontine Gliomas (DIPGs) are deadly paediatric brain tumours where needle biopsies help guide diagnosis and targeted therapies. To address spatial heterogeneity, here we analyse 134 specimens from various neuroanatomical structures of whole autopsy brains from nine DIPG patients. Evolutionary reconstruction indicates histone 3 (H3) K27M-including H3.2K27M-mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis. These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1). Later oncogenic alterations arise in sub-clones and often …

Epidural Hematoma Treated Conservatively: When To Expect The Worst, Julie Lamoureux

All Publications

Background: The Brain Trauma Foundation’s 2006 surgical guidelines have objectively defined the epidural hematoma (EDH) patients who can be treated conservatively. Since then, the literature has not provided adequate clues to identify patients who are at higher risk for EDH progression (EDHP) and conversion to surgical therapy. The goal of our study was to identify those patients.

Methods: We carried a retrospective review over a 5-year period of all EDH who were initially triaged for conservative management. Demographic data, injury severity and history, neurological status, use of anticoagulants or anti-platelets, radiological parameters, conversion to surgery and its timing, and Glasgow …

Looking To The Future Of Stroke Treatment: Combining Recanalization And Neuroprotection In Acute Ischemic Stroke, Michael E. Maniskas

Theses and Dissertations--Neuroscience

Stroke is the 5^th leading cause of death in the U.S. with 130,000 deaths and around 800,000 affected annually. Currently, there is a significant disconnect between basic stroke research and clinical stroke therapeutic needs. Few animal models of stroke target the large vessels that produce cortical deficits seen in the clinical setting. Also, current routes of drug administration, intraperitoneal and intravenous, do not mimic the clinical route of intra-arterial drug administration. To bridge this divide, we have retro-engineered a mouse model of stroke from the current standard of care for emergent large vessel occlusion (ELVO) stroke, endovascular thrombectomy, to …

Changes In The Plasma Proteome At Asymptomatic And Symptomatic Stages Of Autosomal Dominant Alzheimer's Disease, Julia Muenchhoff, Anne Poljak, Anbupalam Thalamuthu, Veer Gupta, Pratishtha Chatterjee, Mark Raftery, Colin Masters, John Morris, Randall Bateman, Anne Fagan, Ralph Martins, Perminder Sachdev

Research outputs 2014 to 2021

The autosomal dominant form of Alzheimer's disease (ADAD) is far less prevalent than late onset Alzheimer's disease (LOAD), but enables well-informed prospective studies, since symptom onset is near certain and age of onset is predictable. Our aim was to discover plasma proteins associated with early AD pathology by investigating plasma protein changes at the asymptomatic and symptomatic stages of ADAD. Eighty-one proteins were compared across asymptomatic mutation carriers (aMC, n = 15), symptomatic mutation carriers (sMC, n = 8) and related noncarriers (NC, n = 12). Proteins were also tested for associations with cognitive measures, brain amyloid deposition and glucose …

Prenatal Nicotine Exposure As A Teratogen In Neurological Pathways, Monica Grover

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Attention-deficit/hyperactivity disorder (ADHD) is the most heritable and commonly diagnosed childhood psychiatric disorder with 4% of all children being diagnosed with this disorder. Prenatal smoking has been found to be a risk factor for ADHD, a disorder that has been believed to be linked to the fluctuation of dopamine levels. Prenatal nicotine exposure in the second trimester influences dopaminergic neurological pathways by altering dopamine release levels. The altered dopamine levels make the fetus brain more sensitive to the nicotine, causing the nicotine exposure to be more dangerous in causing ADHD symptoms. Prenatal nicotine exposure alters the neurological pathway of the …

Ketogenic Diet Decreases Emergency Room Visits And Hospitalizations Related To Epilepsy., Husam R. Kayyali, Anastasia Luniova, Ahmed Abdelmoity

Manuscripts, Articles, Book Chapters and Other Papers

Background. Approximately, one-third of patients with epilepsy are refractory to pharmacological treatment which mandates extensive medical care and imposes significant economic burden on patients and their societies. This study intends to assess the impact of the treatment with ketogenic diet (KD) on reducing seizure-related emergency room visits and hospitalizations in children with refractory epilepsy. Methods. This is a retrospective review of children treated with the KD in one tertiary center. We compared a 12 months' period prior to KD with 12 months after the diet was started in regard to the number of emergency department (ED) visits, hospitalizations, …