Congenital, Hereditary, and Neonatal Diseases and Abnormalities Commons^™

The Impact Of Vitamin Supplementation (D, B12, B9) On Behaviors Associated With Autism Spectrum Disorder, Rohan Mehra

Rowan-Virtua Research Day

Background: One in 36 children in the United States are diagnosed with Autism Spectrum Disorder (ASD). Although heritability of the condition ranges from 40 to 80%, other factors such as vitamin levels, may have a significant impact on the risk of development. These vitamins include D, B12, and B9.

Purpose: To assess the impact vitamin supplementation has on behaviors associated with ASD, and to determine which specific aspects of ASD may be improved with vitamin supplementation.

Methods: A literature review was performed. The search was utilized PubMed, JSTOR and Web of Science. Keyword strings included: “Vitamin D B12 B9 folate …

Gut Microbiome And Nutrition Interplay In Regulating And Improving Autism Spectrum Disorder Related Social Symptoms, Irenonsen Juliet Eigbe, Christian Moya Gamboa, Jana Gjini, Jaydeep Mukherjee, Susrut Dube

Rowan-Virtua Research Day

The composition of the gut microbiome has been shown to play a role in the onset of neurological disorders, including Autism Spectrum Disorder(ASD). A small variety of recent research articles identify a possible link between onset and severity of ASD related behaviors and the composition of the gut microbiome. The purpose of this review is to identify gaps in the current understanding of the role that nutrition plays in changing the gut microbiome and subsequently altering the onset and severity of behavioral phenotypes in children with ASD. Inclusion criteria comprises peer-reviewed publications relating to children with autism. Exclusion criteria consists …

Digital Clock Drawing As An Alzheimer's Disease Susceptibility Biomarker: Associations With Genetic Risk Score And Apoe In Older Adults, L I Thompson, M Cummings, S Emrani, David J. Libon, A Ang, C Karjadi, R Au, C Liu

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia in older adults, but most people are not diagnosed until significant neuronal loss has likely occurred along with a decline in cognition. Non-invasive and cost-effective digital biomarkers for AD have the potential to improve early detection.

OBJECTIVE: We examined the validity of DCTclockTM (a digitized clock drawing task) as an AD susceptibility biomarker.

DESIGN: We used two primary independent variables, Apolipoprotein E (APOE) ε4 allele carrier status and polygenic risk score (PRS). We examined APOE and PRS associations with DCTclockTM composite scores as dependent measures.

SETTING: We used existing data …

Differential Degeneration Of Neurons In A Mouse Model Of Canavan Disease, Vibha Chauhan, Quy Nguyen, Jeremy Francis, Paola Leone

Rowan-Virtua Research Day

Canavan disease (CD) is an inherited leukodystrophy caused by inactivating mutations to the glial enzyme aspartoacylase (ASPA). ASPA catabolizes neuronal N-acetylaspartate (NAA) into free acetate and aspartate and loss of this function results in the chronic elevation of non-catabolized NAA and the failure of developmental myelination. Elevated NAA is thought to cause damage to myelin and myelin-producing cells (oligodendrocytes, but the viability of neurons in CD is relatively unexplored. We compare here the progressive degeneration of neurons in two regions of the CD mouse brain, the thalamus and the cortex, distinguished by differing degrees of vacuolation, and show that the …

Kearns-Sayre Syndrome: Two Case Reports And A Review For The Primary Care Physician., Chad Richmond, Leonard Powell, Zachary D. Brittingham, Alison Mancuso

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Kearns-Sayre syndrome (KSS) is a mitochondrial encephalopathic disorder. Because mitochondria are ubiquitous organelles that are present in almost every human tissue, their dysfunction can affect nearly any organ system and give rise to a wide range of clinical characteristics. 1: As is the case with most diseases associated with mitochondrial DNA (mtDNA) mutations, the clinical features of KSS were defined before modern molecular genetic classifications emerged. 2: The exact prevalence of KSS is unknown; however, estimates place it at about 1:100,000 people. Although it is a rather rare syndrome, the ability to recognize or consider KSS as part of a …

The Role Of The Nlrp3 Inflammasome In Alzheimer's Disease, Ethan S. Terman

Undergraduate Research Posters

This study examines the consequences of Alzheimer’s in rat and mice test subjects. The goal is to identify the effects of certain NLRP3 inhibiting drugs and to see if there are any noticeable effects in regards to impeding the pathological development of Alzheimer’s disease. The results are visualized by implementing the immunohistochemical process to identify neurodegeneration in the brain and to assess the expression levels of amyloid beta as an indicator of Alzheimer’s pathology. Other tests are also conducted on these transgenic mice to gauge cognitive functioning levels during the onset of their disease, those being behavior tests, but not …

Alzheimer's And Patient Caregiver Burnout: A Review Of The Literature, Madeline Hekeler

James Madison Undergraduate Research Journal (JMURJ)

The term “silent epidemic” is fitting for Alzheimer’s disease (AD), as its negative impact is widely felt but rarely discussed. Burnout among AD caregivers has become an epidemic of its own as caregivers experience an increase in health risks, stress, and financial burden. This literature review focuses on caregiver burnout and how imperative it is that caregivers are better supported in their role. Researchers have developed instruments to assess and intervene in caregiver burnout that have shown effectiveness among caregivers and their families.Nevertheless, further longitudinal research is warranted regarding more effective interventions, including stress management and social support mechanisms.

Telemedicine Consultation To Assess Neonatal Encephalopathy In Rural Community Hospitals And Tertiary Care Centers, Rachel Coffey, Misty Melendi, Anya K. Cutler, Alexa K. Craig

Journal of Maine Medical Center

Introduction: Teleconsultation is used in tertiary care hospitals to evaluate neonatal encephalopathy. Neonates born in community hospitals, however, often experience delayed evaluation due to transport to the tertiary care center. We studied teleconsultations in community hospitals to decrease this disparity.

Methods: Prospective observational study in 9 community hospitals and 1 neonatal intensive care unit. Inclusion criteria: gestational age greater than or equal to 35 weeks and one of the following: umbilical cord pH less than or equal to 7.2, 5-minute Apgar less than 7, prolonged respiratory support, perinatal event, or abnormal neurological exam. We performed synchronized, unscheduled telemedicine consults with …

In Pursuit: A Mother’S Account Of Her Son’S Rare Disease Diagnosis Journey, Anne M. Jones

Journal of Patient-Centered Research and Reviews

A personal account from a mother’s perspective on her undiagnosed son’s medical journey over almost 6 years toward a diagnosis of a rare genetic variant in mitogen-activated protein kinase 8 interacting protein 3 (MAPK8IP3) resulting in neurodevelopment disorder.

Comparing Open And Fetoscopic Fetal Surgical Repairs Of Myelomeningocele, Kyra Isaacs

Capstone Showcase

Introduction: There have been great advances in the treatment of myelomeningocele (MMC) spina bifida in the past 20 years. An open surgical repair in-utero has been shown to reduce mortality and morbidity, specifically decreasing the rate of shunt placement and hindbrain herniation compared to a postnatal surgical approach. However, this surgery introduced risks to the mother that were never a consideration in previous surgical approaches.

Methods: This paper compares research on new minimally invasive fetoscopic surgical techniques to open fetal surgery in the prenatal repair of MMC. Searches in PubMed and Clinical Key were conducted to produce papers published on …

Is It Fair To Compare? A Patient And Family Experience Of Two Healthcare Systems And Neurosurgical Teams Within A Two-Week Period, Laura Miller Cpxp

Patient Experience Journal

As the mother of a 28-year-old son with cerebral palsy and hydrocephalus, and as a healthcare consultant focused on patient experience and professional development, I have a unique perspective and skill set. Recently he experienced symptoms that included an excruciating headache, neck pain and lethargy. Fearing his ventriculoperitoneal shunt had malfunctioned, he went to the emergency room and was later admitted on the neuro inpatient floor for a three-day hospitalization. His original shunt had been placed in 1991, and he never had an issue with until August 2018. While in the hospital, he was informed that he was no longer …

Neurodevelopmental Outcomes Of Infantile Hydrocephalus: An Fmri Case Study, Ikhlas Ahmed Hashi

Electronic Thesis and Dissertation Repository

Ventricle dilatation caused by infantile hydrocephalus may result in extensive damage of the posterior cortex (parietal and occipital lobes). We hypothesize that pathological changes in the development of the posterior cortex can be linked to non-verbal learning disabilities in children with previous infantile hydrocephalus. This case study will investigate the neurodevelopmental outcomes of 3 treated hydrocephalus patients, when compared to a group of healthy control children (n = 12). Within the hydrocephalus group, patients displayed differences in non-verbal test performance as well as parietal brain activation during an fMRI number comparison task. We associated these differences with clinical variables such …

Recommendations For The Design Of Therapeutic Trials For Neonatal Seizures., Janet S. Soul, Ronit Pressler, Marilee Allen, Geraldine Boylan, Heike Rabe, Ron Portman, Pollyanna Hardy, Sarah Zohar, Klaus Romero, Brian Tseng, Varsha Bhatt-Mehta, Cecil Hahn, Scott Denne, Stephane Auvin, Alexander Vinks, John Lantos, Neil Marlow, Jonathan M. Davis, International Neonatal Consortium

Manuscripts, Articles, Book Chapters and Other Papers

Although seizures have a higher incidence in neonates than any other age group and are associated with significant mortality and neurodevelopmental disability, treatment is largely guided by physician preference and tradition, due to a lack of data from well-designed clinical trials. There is increasing interest in conducting trials of novel drugs to treat neonatal seizures, but the unique characteristics of this disorder and patient population require special consideration with regard to trial design. The Critical Path Institute formed a global working group of experts and key stakeholders from academia, the pharmaceutical industry, regulatory agencies, neonatal nurse associations, and patient advocacy …

Weighted Pathway Genetic Load Analysis Of Hyperbilirubinemic Infants Indicates A Potential Genetic Component For Susceptibility To Bilirubin Neurotoxicity, Sean M. Riordan, Jean-Baptiste Lepichon, Steven Shapiro, John Cowden, Monica Villagullen, Laurence Thielemans, Dina Villanueva Garcia, Jesus Aguirre-Hernandez

Posters

Severe kernicterus spectrum disorder (KSD) is described as motor and auditory deficits resulting from brain damage caused by hyperbilirubinemia. The severity of HB does not always predict the severity of injury. The lack of a strong monogenetic link to susceptibility suggests bilirubin-induced brain damage may be due to impaired bilirubin response pathways. This poster describes work to use a modified pathway genetic load (mPGL) score method to perform a targeted genetic analysis of whole exome data from patients with various degrees of neonatal HB, with an ultimate goal of developing a neonatal screen to susceptibiltiy to bilirubin neurotoxicity.

Total And Free Plasma Bilirubin And Clinical Outcomes In Severe Hyperbilirubinemia, Sean M. Riordan, Jean-Baptiste Lepichon, Steven Shapiro, Tina Slusher, Fatima Abdullahi, Hafsat M. Suleiman, Victor C. Pam, Mamu B. Samuel, Christopher S. Yilgwan, Christian Isichei, Idris Y. Mohammed

Posters

Acute bilirubin encephalopathy (ABE) and kernicterus spectrum disorder (KSD) have become relatively uncommon in high income countries but remain a major cause of morbidity and mortality in low- and middle-income countries. To better understand the relationship between free (Bf) and total (TB) bilirubin levels and the development of ABE and KSD we followed infants born in three large tertiary centers in northern and central Nigeria (Jos, Kano and Zaria).

Acute Bilirubin Encephalopathy And Its Progression To Kernicterus: Current Perspectives, Fatima Usman, Udochukwu Michael Diala, Steven Shapiro, Jean-Baptist Lepichon, Tina M. Slusher

Manuscripts, Articles, Book Chapters and Other Papers

Acute bilirubin encephalopathy (ABE) remains a significant cause of morbidity and mortality throughout the world, especially in low-middle-income countries where it can account for up to 15% of neonatal death. The pathophysiology of this acute life-threatening event of infancy and its potential evolution to kernicterus remain poorly understood. In this review, we start by reviewing the terminology of hyperbilirubinemia and its clinical consequences, ABE and later kernicterus spectrum disorder (KSD). We then review the pathogenesis of ABE and discuss clinical factors that can contribute to its pathogenicity. We examine in detail the clinical correlates of ABE and KSD. We present …

Factors Associated With End-Of-Life Planning In Huntington Disease., Nancy R Downing, Siera Goodnight, Sena Chae, Joel S Perlmutter, Michael Mccormack, Elizabeth Hahn, Stacey K Barton, Noelle Carlozzi

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

OBJECTIVE: Knowledge of one's gene status for adult onset conditions provides opportunity to make advance end-of-life (EOL) plans. The purposes of these analyses were to (1) determine the prevalence of EOL plans, including advance directives (ADs) among persons across 3 stages of Huntington disease (HD) and (2) examine factors associated with having ADs in this sample.

METHODS: Data are from 503 participants in the HD Quality of Life study. Participants completed an online health-related quality-of-life survey that included questions regarding EOL planning and self-reported HD symptoms. Frequencies were calculated for EOL planning by the HD stage. Bivariate analysis and logistic …

Evaluating Cognition In Individuals With Huntington Disease: Neuroqol Cognitive Functioning Measures, Jin-Shei Lai, Siera Goodnight, Nancy R Downing, Rebecca E Ready, Jane S Paulsen, Anna L Kratz, Julie C Stout, Michael K Mccormack, David Cella, Christopher Ross, Jenna Russell, Noelle E Carlozzi

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

PURPOSE: Cognitive functioning impacts health-related quality of life (HRQOL) for individuals with Huntington disease (HD). The Neuro-QoL includes two patient-reported outcome (PRO) measures of cognition-Executive Function (EF) and General Concerns (GC). These measures have not previously been validated for use in HD. The purpose of this analysis is to evaluate the reliability and validity of the Neuro-QoL Cognitive Function measures for use in HD.

METHODS: Five hundred ten individuals with prodromal or manifest HD completed the Neuro-QoL Cognition measures, two other PRO measures of HRQOL (WHODAS 2.0 and EQ5D), and a depression measure (PROMIS Depression). Measures of functioning The Total …

Suicidal Ideation Assessment In Individuals With Premanifest And Manifest Huntington Disease., Melissa Wesson, Nicholas R Boileau, Joel S Perlmutter, Jane S Paulsen, Stacey K Barton, Michael K Mccormack, Noelle E Carlozzi

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: Huntington disease (HD) is associated with increased risk of suicide.

OBJECTIVE: This study compares suicide ideation in HD to the general population, assesses factors associated with increased prevalence of suicidal thoughts, and compares clinician-rated to self-reported assessments of suicidal ideation.

METHODS: We examined 496 participants with premanifest or manifest HD. Clinician-rated suicidal ideation was measured using the Problem Behaviors Assessment - short form. Self-reported ideation was measured using two items from the HDQLIFE Concern with Death and Dying item bank. Independent sample t-tests were conducted to compare the prevalence of suicidal thoughts between our HD sample and the U.S. …

Use Of The Ketogenic Diet In The Neonatal Intensive Care Unit-Safety And Tolerability., Lindsey M. Thompson, Erin Day Fecske, Mohammad Salim, Ara Hall

Manuscripts, Articles, Book Chapters and Other Papers

Drug-resistant epilepsy poses a challenge in neonatal patients, especially those in the neonatal intensive care unit (NICU), who have various secondary comorbidities. We present results of four children with a history of drug-resistant epilepsy for whom a ketogenic diet was initiated and used in the NICU. A nonfasting induction into ketosis over 1-2 weeks was utilized, with gradual increases in the ketogenic ratio every 2-3 days. Data were collected retrospectively from a database, which included medical history, daily progress notes, relevant laboratory data, and imaging and diagnostic information. The ketogenic diet was well tolerated in all cases. The most common …

Abnormal Glycosylation In Joubert Syndrome Type 10., Megan S Kane, Mariska Davids, Michelle R Bond, Christopher J Adams, Megan E Grout, Ian G Phelps, Gilbert Vezina, +Several Additional Authors

Neurology Faculty Publications

BACKGROUND: The discovery of disease pathogenesis requires systematic agnostic screening of multiple homeostatic processes that may become deregulated. We illustrate this principle in the evaluation and diagnosis of a 5-year-old boy with Joubert syndrome type 10 (JBTS10). He carried the OFD1 mutation p.Gln886Lysfs*2 (NM_003611.2: c.2656del) and manifested features of Joubert syndrome.

METHODS: We integrated exome sequencing, MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes, and full clinical evaluation of the proband. Analyses of cilia formation and lectin staining were performed by immunofluorescence. Measurement of cellular nucleotide sugar levels was performed with high-performance anion-exchange chromatography with pulsed amperometric …

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 …

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. …

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 …

Associations Between Performance On The Rey-Osterrieth Complex Figure And Regional Brain Volumes In Children With And Without Velocardiofacial Syndrome, Kevin M. Antshel, Jena Peebles, Nuria Abdulsabur, Anne Marie Higgins, Nancy Roizen, Robert J. Shprintzen, Wanda Fremont, Robert Natasi, Wendy R. Kates

Communication Disorders Faculty Publications

Ninety-two children with velocardiofacial syndrome (VCFS), a genetic disorder caused by a microdeletion of chromosome 22q11.2 and an age, race, and gender-ratio comparable sample of 59 control participants were included in the project. Participants received an MRI as well as a comprehensive neuropsychological battery; the primary outcome measure in the current report is the Rey-Osterrieth Complex Figure (ROCF). Children with VCFS performed less well on the ROCF and have lower whole brain volume compared to controls. After controlling for whole brain volume differences, children with VCFS have bilaterally less parietal lobe gray and white matter yet more frontal lobe white …