Neurology Commons^™

Electrophysiological Signatures Of Spatial Boundaries In The Human Subiculum., Sang Ah Lee, Jonathan F. Miller, Andrew J. Watrous, Michael R. Sperling, Ashwini Sharan, Gregory A. Worrell, Brent M. Berry, Joshua P. Aronson, Kathryn A. Davis, Robert E. Gross, Bradley Lega, Sameer Sheth, Sandhitsu R. Das, Joel M. Stein, Richard Gorniak, Daniel S. Rizzuto, Joshua Jacobs

Department of Radiology Faculty Papers

Environmental boundaries play a crucial role in spatial navigation and memory across a wide range of distantly related species. In rodents, boundary representations have been identified at the single-cell level in the subiculum and entorhinal cortex of the hippocampal formation. Although studies of hippocampal function and spatial behavior suggest that similar representations might exist in humans, boundary-related neural activity has not been identified electrophysiologically in humans until now. To address this gap in the literature, we analyzed intracranial recordings from the hippocampal formation of surgical epilepsy patients (of both sexes) while they performed a virtual spatial navigation task and compared …

Transcriptional Regulatory Networks Underlying Gene Expression Changes In Huntington's Disease., Seth A Ament, Jocelynn R Pearl, Jeffrey P Cantle, Robert M Bragg, Peter J Skene, Sydney R Coffey, Dani E Bergey, Vanessa C Wheeler, Marcy E Macdonald, Nitin S Baliga, Jim Rosinski, Leroy E Hood, Jeffrey B Carroll, Nathan D Price

Articles, Abstracts, and Reports

Transcriptional changes occur presymptomatically and throughout Huntington's disease (HD), motivating the study of transcriptional regulatory networks (TRNs) in HD We reconstructed a genome-scale model for the target genes of 718 transcription factors (TFs) in the mouse striatum by integrating a model of genomic binding sites with transcriptome profiling of striatal tissue from HD mouse models. We identified 48 differentially expressed TF-target gene modules associated with age- and CAG repeat length-dependent gene expression changes in

The Current Trend Of The Translational Research Paradigm., Paul J Choi, R Shane Tubbs, Rod J Oskouian

Articles, Abstracts, and Reports

The translational research paradigm is a process of discovering basic science concepts and applying the knowledge in clinical practice, aiming to improve patient care. The stages involved in the paradigm form a complex network of shared knowledge amongst research collaborators, including patients. This nature of the paradigm allows those involved to work together effectively. However, the translational research paradigm is often overlooked by many scientists, educators, and research institutions. Hence, a large amount of comprehensive and hugely invested research projects fail to make a scientific impact. We aim to outline and describe this paradigm in order to aid in the …

Mitochondrial Transplantation Strategies As Potential Therapeutics For Central Nervous System Trauma, Jenna L. Gollihue, Samir P. Patel, Alexander G. Rabchevsky

Spinal Cord and Brain Injury Research Center Faculty Publications

Mitochondria are essential cellular organelles critical for generating adenosine triphosphate for cellular homeostasis, as well as various mechanisms that can lead to both necrosis and apoptosis. The field of “mitochondrial medicine” is emerging in which injury/disease states are targeted therapeutically at the level of the mitochondrion, including specific antioxidants, bioenergetic substrate additions, and membrane uncoupling agents. Consequently, novel mitochondrial transplantation strategies represent a potentially multifactorial therapy leading to increased adenosine triphosphate production, decreased oxidative stress, mitochondrial DNA replacement, improved bioenergetics and tissue sparing. Herein, we describe briefly the history of mitochondrial transplantation and the various techniques used for both in …

Biomarker And Clinical Trial Design Support For Disease-Modifying Therapies: Report Of A Survey Of The Eu/Us: Alzheimer's Disease Task Force, Jeffrey Cummings, Nick Fox, Bruno Vellas, Paul Aisen, Guogen Shan

Environmental & Global Health Faculty Research

BACKGROUND: Disease-modifying therapies are urgently needed for the treatment of Alzheimer’s disease (AD). The European Union/United States (EU/US) Task Force represents a broad range of stakeholders including biopharma industry personnel, academicians, and regulatory authorities. OBJECTIVES: The EU/US Task Force represents a community of knowledgeable individuals who can inform views of evidence supporting disease modification and the development of disease-modifying therapies (DMTs). We queried their attitudes toward clinical trial design and biomarkers in support of DMTs. DESIGN/SETTING/PARTICIANTS: A survey of members of the EU/US Alzheimer’s Disease Task Force was conducted. Ninety-three members (87%) responded. The details were analyzed to understand what …

Variant Intestinal-Cell Kinase In Juvenile Myoclonic Epilepsy, J. N. Bailey, L. De Nijs, D. Bai, T. Suzuki, H. Miyamoto, M. Tanaka, C. Patterson, Y.-C. Lin, M. T. Medina, M. E. Alonso, J. M. Serratosa, R. M. Durón, Viet-Hong Nguyen, J. E. Wight, I. E. Martínez‑Juárez, A. Ochoa, A. Jara-Prado, L. Guilhoto, Y. Molina, E. M. Yacubian, M. López‑Ruiz, Y. Inoue, S. Kaneko, S. Hirose, M. Osawa, H. Oguni, S. Fujimoto, T. M. Grisar, J. M. Stern, K. Yamakawa, B. Lakaye, A. V. Delgado-Escueta

Pharmacy Faculty Articles and Research

BACKGROUND

In juvenile myoclonic epilepsy, data are limited on the genetic basis of networks promoting convulsions with diffuse polyspikes on electroencephalography (EEG) and the subtle microscopic brain dysplasia called microdysgenesis.

METHODS

Using Sanger sequencing, we sequenced the exomes of six members of a large family affected with juvenile myoclonic epilepsy and confirmed cosegregation in all 37 family members. We screened an additional 310 patients with this disorder for variants on DNA melting-curve analysis and targeted real-time DNA sequencing of the gene encoding intestinal-cell kinase (ICK). We calculated Bayesian logarithm of the odds (LOD) scores for cosegregating variants, odds …

Emerging Cellular Therapies For Glioblastoma Multiforme., Paul J Choi, R Shane Tubbs, Rod J Oskouian

Articles, Abstracts, and Reports

Glioblastoma multiforme (GBM) is the most common type of malignant primary brain cancer in adults. It is composed of highly malignant cells that display metastatic and angiogenic characteristics, making it resistant to current first-line chemotherapy with temozolomide, an alkylating agent. Despite many years of research, GBM remains poorly responsive to multiple available therapies, giving GBM patients, who receive the conventional combination of chemoradiotherapies and surgical resection, a dismal prognosis. There is growing evidence that the conventional systemic chemotherapeutic agents for GBM are ineffective in improving the disease progression. We aim to explore the emerging cellular therapies which may play a …

Clinical Feasibility Of Umbilical Cord Tissue-Derived Mesenchymal Stem Cells In The Treatment Of Multiple Sclerosis., Neil H Riordan, Isabela Morales, Giselle Fernández, Nicole Allen, Neal E Fearnot, Michael E Leckrone, Dedra Jones Markovich, Darla Mansfield, Dorita Avila, Amit N Patel, Santosh Kesari, Jorge Paz Rodriguez

Articles, Abstracts, and Reports

BACKGROUND: Multiple sclerosis (MS) is a progressively debilitating neurological condition in which the immune system abnormally erodes the myelin sheath insulating the nerves. Mesenchymal stem cells (MSC) have been used in the last decade to safely treat certain immune and inflammatory conditions.

METHODS: A safety and feasibility study was completed on the use of umbilical cord MSC (UCMSC) as a treatment for MS. In this 1-year study, consenting subjects received seven intravenous infusions of 20 × 10

RESULTS: Twenty subjects were enrolled in this study. No serious adverse events were reported. Of the mild AEs denoted as possibly related to …

Calnexin Is Necessary For T Cell Transmigration Into The Central Nervous System, Amber M. Paul, Joanna Jung, Paul Eggleton, Alison Robinson, Jessica Wang, Nick Gutowski

Publications

In multiple sclerosis (MS), a demyelinating inflammatory disease of the CNS, and its animal model (experimental autoimmune encephalomyelitis; EAE), circulating immune cells gain access to the CNS across the blood-brain barrier to cause inflammation, myelin destruction, and neuronal damage. Here, we discovered that calnexin, an ER chaperone, is highly abundant in human brain endothelial cells of MS patients. Conversely, mice lacking calnexin exhibited resistance to EAE induction, no evidence of immune cell infiltration into the CNS, and no induction of inflammation markers within the CNS. Furthermore, calnexin deficiency in mice did not alter the development or function of the immune …

Use Of Preoperative Apparent Diffusion Coefficients To Predict Brain Tumor Grade, Aneela Darbar, Muhammad Waqas, Syed Faaiz Enam, Shaikh D. Mahmood

Section of Neurosurgery

Introduction: The apparent diffusion coefficient (ADC) sequence is based on the diffusion properties of water molecules within tissues and correlates with tissue cellularity. ADC may have a role in predicting tumor grade for gliomas, and may in turn assist in identifying tumor biopsy sites. The purpose of this investigation was to assess the competence of preoperative ADC values in predicting tumor grades.
Methods: This was a retrospective investigation. We calculated the ADC values in the areas of greatest restriction in solid tumor components, and we recorded the pattern of contrast enhancement. Pathology reports masked to the imaging results were reviewed …

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 …

Amperometric Self-Referencing Ceramic Based Microelectrode Arrays For D-Serine Detection, Diana Campos-Beltrán, Åsa Konradsson-Geuken, Jorge E. Quintero, Lisa Marshall

Neuroscience Faculty Publications

D-serine is the major D-amino acid in the mammalian central nervous system. As the dominant co-agonist of the endogenous synaptic NMDA receptor, D-serine plays a role in synaptic plasticity, learning, and memory. Alterations in D-serine are linked to neuropsychiatric disorders including schizophrenia. Thus, it is of increasing interest to monitor the concentration of D-serine in vivo as a relevant player in dynamic neuron-glia network activity. Here we present a procedure for amperometric detection of D-serine with self-referencing ceramic-based microelectrode arrays (MEAs) coated with D-amino acid oxidase from the yeast Rhodotorula gracilis (RgDAAO). We demonstrate in vitro D-serine recordings with a …

14th Annual Parkview Research Symposium, Michael J. Mirro, Neil Sharma, Tammy Toscos, Roy Robertson Md, Micah Smith Md, Jason Voorhies Md

Presentations and Events

14th Annual Parkview Research Symposium: Innovative Interventions in Healthcare

Objectives

* Discuss latest innovative interventions in informatics, oncology, cardiology, orthopedids and neurosurgery.

* Develop a strategy for efficient diagnosis and treatment planning using the latest innovative techniques and research findings in informatics, oncology, cardiology, orthopedics and neurosurgery.

Rare Case Of Diffuse Spinal Arachnoiditis Following A Complicated Vertebral Artery Dissection, Elias Atallah, Md, Sophia Dang, Sage Rahm, Nohra Chalouhi, Md, Stavropoula Tjoumakaris Md, Robert H. Rosenwasswer Md, Pascal Jabbour Md

Department of Neurosurgery Posters

Spinal arachnoiditis (SA) is an extremely rare and delayed complication of intracranial subarachnoid hemorrhage (SAH). SA is an inflammatory process leading to chronic fibrosis of the spinal cord. Possible pathophysiology is a two-staged disease of initial inflammatory reaction secondary to SAH, followed by a “free interval phase” prior to delayed adhesive phase (i.e. SA). The clinical course can be complicated and is the cause of major morbidity.

Cortical Thinning And Neuropsychiatric Outcomes In Children Exposed To Prenatal Adversity: A Role For Placental Crh?, Curt A. Sandman, Megan M. Curran, Elyssia Poggi Davis, Laura M. Glynn, Kevin Head, Tallie Z. Baram

Psychology Faculty Articles and Research

Exposure to early life adversity may disrupt the development and maturation of neurons and brain circuits, which, in turn, underlie neurodevelopment and mental illnesses. During fetal life, maternal adversity is conveyed to the developing brain via several molecular signals, including the stress hormone corticotropin releasing hormone (CRH). Employing a large well characterized prospective cohort, we find that fetal exposure to placental-origin CRH levels predicts structural and functional brain outcomes in children. Specifically, elevated placental CRH levels portend thinning of selective cortical regions of exposed individuals, with commensurate cognitive and emotional deficits. Notably, the relations of placental-origin CRH to cortical thinning …

Impact Of Supplemental Oxygen On Obstructive Sleep Apnea Of Infants, Piyush Das, R Kashyap, S Kotagal

Articles

Abstract: Treatment options may be limited for infants with obstructive sleep apnea when there is no surgically correctable upper airway lesion. We therefore evaluated, retrospectively, the efficacy of low-flow oxygen as a therapeutic option for infant obstructive sleep apnea. We reviewed the medical charts of 23 infants who had undergone a therapeutic trial of low-flow oxygen during polysomnography. Split-night polysomnography was used in 21/23 subjects while 2/23 had undergone two separate, full-night polysomnography sleep architecture and respiratory findings on the baseline polysomnogram segment that was obtained in room air were compared with the segment on low-flow oxygen (0.25–1 L/min). Wilcoxon …

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 Departmental Research

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 Departmental Research

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 …

Importance Of Bioethics In Healthcare, Rizwan Taj, Asima Khan

Pakistan Journal of Neurological Sciences (PJNS)

Healthcare ethics deals with ethical issues in health care, medicine and science.Ethical codes and its application have long history from ancient era. In presentscenario, both advancement in medical field and the challenges are increasing in same pace for healthcare providers to deal with ethical issues. Therefore, the undoubtedly important role of bioethics emerges here. Bioethics in healthcare brings understanding and knowledge among healthcare professionals about medical practice.Stressing upon the ethical aspects of bioethics, medical professionals are capable oftagging along ethical codes while practicing especially while dealing with issues. As ethical tribulations are linked with issues in medical care, so by …

Acute Disseminated Encephalomyelitis In A Middle Age Female, Hina Mushtaq, Maria Qureshi, Irfan Ahsan

Pakistan Journal of Neurological Sciences (PJNS)

Acute disseminated encephalomyelitis (ADEM) is an autoimmune condition that predominately involve demyelination of the white matter of the brain and spinal cord. It resembles other acute demyelinating syndromes like multiple sclerosis and most often presents in childhood.This is a case of a 52-year woman, presented with lower limb weakness, confusion and spasticity throughout the body with no preceding illness. CSF showed increased proteins with no oligoclonal bands. MRI Brain showed abnormal high intensity areas in bilateral parietal, periventricular region, with no contrast enhancement. She was given 1gram iv methylprednisolone based on the diagnosis of ADEM and responded well.