DOCSLIB.ORG

Recent Advances in Modelling of Cerebellar Ataxia Using Induced Pluripotent Stem Cells Maggie M

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Recent Advances in Modelling of Cerebellar Ataxia Using Induced Pluripotent Stem Cells Maggie M Wong MMK, Watson LM, Becker EBE. J Neurol Neuromedicine (2017) 2(7): 11-15 Neuromedicine www.jneurology.com www.jneurology.com Journal of Neurology & Neuromedicine Mini Review Open Access Recent advances in modelling of cerebellar ataxia using induced pluripotent stem cells Maggie M. K. Wong1, Lauren M. Watson1 and Esther B. E. Becker1* 1Department of Physiology, Anatomy and Genetics, University of Oxford, United Kingdom Article Info ABSTRACT Article Notes The cerebellar ataxias are a group of incurable brain disorders that are caused Received: May 15, 2017 primarily by the progressive dysfunction and degeneration of cerebellar Purkinje Accepted: July 10, 2017 cells. The lack of reliable disease models for the heterogeneous ataxias has hindered the understanding of the underlying pathogenic mechanisms as well *Correspondence: Dr. Esther B. E. Becker as the development of effective therapies for these devastating diseases. Recent University of Oxford, Department of Physiology, Anatomy and advances in the field of induced pluripotent stem cell (iPSC) technology offer Genetics, Sherrington Road, Oxford OX1 3PT, United Kingdom, new possibilities to better understand and potentially reverse disease pathology. Email: [email protected] Given the neurodevelopmental phenotypes observed in several types of ataxias, iPSC-based models have the potential to provide significant insights into disease © 2017 Becker EBE. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License progression, as well as opportunities for the development of early intervention therapies. To date, however, very few studies have successfully used iPSC-derived Keywords cells to model cerebellar ataxias. In this review, we focus on recent breakthroughs iPSC in generating human iPSC-derived Purkinje cells. We also highlight the future Cerebellum challenges that will need to be addressed in order to fully exploit these models for Ataxia the modelling of the molecular mechanisms underlying cerebellar ataxias and the Disease modelling development of effective therapeutics. Purkinje cells Development Neurodegeneration Cerebellar ataxias The cerebellar ataxias are a clinically and genetically diverse group of neurological disorders that primarily affect the cerebellum. Characterized by a progressive loss of motor coordination, other symptoms include dysarthria and disturbance of eye movements1. Cerebellar ataxias may be acquired or inherited, with hereditary ataxias toclassified date . intoAmong autosomal these, the dominant, autosomal autosomal recessive recessive, disorders X-linked Friedreich or mitochondrial2-4 forms. Over 60 genetic subtypes have been identified dominant polyglutamine spinocerebellar ataxias (SCAs) are the ataxia (FRDA) and ataxia-telangiectasia (A-T), as well as the autosomal heterogeneity, emerging evidence points to the existence of common pathogenicmost studied mechanisms forms of ataxias. that mayDespite be significantshared by clinicalseveral andgenetically genetic distinct forms of cerebellar ataxias (reviewed in ). However, it is still unclear how the proposed pathological pathways5-8 ultimately result in cerebellar dysfunction and degeneration, predominantly affecting Purkinje cells. neurodegenerative disorders. The heterogeneous nature of the cerebellar Understanding disease mechanisms is key to treating of reliable disease models have, however, hampered our understanding ofataxias the molecular combined disease with the mechanisms unavailability underlying of human brain cerebellar tissue andataxias the lackand Page 11 of 15 Wong MMK, Watson LM, Becker EBE. J Neurol Neuromedicine (2017) 2(7): 11-15 Journal of Neurology & Neuromedicine thus, the development of effective therapies. Although mouse models of several cerebellar ataxias, including FRDA and SCAs, have provided valuable insights into the morphologycells expressed with mature an extensively PC markers arborized including dendritic L7/PCP2 tree. pathophysiology of these disorders (reviewed in9), many and GRID2, and possessed a characteristic Purkinje cell questions remain about the observed species differences in disease phenotypes and the effectiveness of potential matureMoreover,22,23 these. cells displayed the distinctive firing pattern drugs in clinical trials. To help translate research from of Purkinje cells, suggesting that they were functionally Wang et al. animal models into novel treatments for ataxia patients, with human foetal used acerebellar similar self-inductive slices . Although approach these to produce Purkinje cells from human 24iPSCs co-cultured Theit is essentialcurrent obstacles to validate might findings be overcomein the relevant by exploiting affected human cell types, particularly in cerebellar Purkinje cells. and were electrically active, they did not possess the recently developed human induced pluripotent stem cell cells appeared to display Purkinje cell-specific markers (iPSC) technology and neuronal differentiation protocols. Generation of cerebellar neurons using human iPSCs duecharacteristic to associated morphology ethical issues. of mature Purkinje cells. Moreover, this protocol is likely to be limited in its uptake Most recently, the Mugumura group used a very similar allowed for the robust reprogramming of human somatic cellsMajor into advancesiPSCs in the field of stem cell technology have cells from iPSCs, but with the inclusion of two additional 10-12 approach to their original method to generate Purkinje neuronal subtypes and. Human other affectedataxia patient-specific cell types in cerebellar iPSCs, ataxias,which can would subsequently be an ideal toolbe differentiatedfor studying the into pathogenic specific mediumgrowth 25factors (brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3)) in their maturation neurons possessed. After co-culture extensively with branched mouse primary dendritic granule trees drugmechanisms screening in inhuman vitro and disease-relevant neurons, cell precursors for 75 days, the human iPSC-derived and might also be highly13,14 valuable for high-throughput to differentiate in vitro, owing. Cerebellar to their largePurkinje size, cellscomplex are throughoutwith a thick soma stem, and characteristic dendrites, andof mature the synaptic Purkinje receptor cells, particularly vulnerable in cerebellar ataxia but difficult GRID2and expressed on dendritic the mature spines. PC-specificThus, this markersprotocol L7/PCP2not only of maturation offers a shorter and more feasible protocol to generate beenmorphology, achieved unique8,13 recently firing and properties are reviewed and below. extensive period . However, significant breakthroughs have that more closely resemble those in vivo. The generation of cerebellar neurons from human iPSCs Purkinje cells, but also produces more mature looking PCs aims to recapitulate the complex in vivo molecular events remain to be addressed before researchers can fully exploit circuit formation during human embryogenesis . Early Despite this significant progress, a number of challenges thatprotocols direct attempted the specification cerebellar of differentiation cerebellar neurons, using15-17 either and neurons allow for close monitoring of their individual mouse or human embryonic stem cells (ESCs) . These developmentiPSC-based cerebellar throughout models. differentiation; Dissociated however, cultures their of approaches sought to mimic the in vivo signals18-21 involved maturation and survival is limited compared to neurons in early cerebellar development by delivering inductive signals, including bone morphogenic proteins, mitogens of appropriate support in in vitro cultures . Moreover, diseasedeveloping phenotypes in the embryonic affecting synapsebrain, likely formation, due26,27 to dendritic the lack differentiation process. However, the resulting cerebellar retraction and neuronal migration , which may only arise and neurotrophins, in a step-wise fashion throughout the from interactions between cells 28,29and their environment, and a relatively high number of cerebellar granule cells . cultures only contained a small proportion of Purkinje cells18,20 Muguruma et al. adopted a different approach, which mayA be way lost forward in these totwo-dimensional overcome this cultures.limitation might be in vitro structures patterning, by adding a combination of only three factors that include multiple cell types and mimic the in vivo aimed to induce endogenous signals mimicking cerebellar architecturethe use of organoids, of an organ self-organizing30. Despite the relative success 22,23. Followed (insulin, fibroblast growth factor 2 (Fgf2) and cyclopamine) cerebral cortex (reviewed in30,31), only one study has to floating aggregates of mouse or human ESCs thusin generating far reported organoids the generation mimicking of cerebellardevelopment organoids. of the by dissociation, fluorescence-activated cell sorting for Muguruma et al. showed that the addition of Fgf19 and derivedKIRREL2/NEPH3-positive granule cell precursors, Purkinje this cell method progenitors, resulted and in subsequent co-culture with mouse primary rhombic lip- than had previously been achieved. The differentiated stromal cell-derived factor 1 (Sdf1) during differentiation the generation of Purkinje cells at a much higher efficiency promoted the self-organisation of human ESCs into polarized three-layer structures reminiscent of the human Page 12 of 15 Wong MMK, Watson LM, Becker EBE. J Neurol Neuromedicine (2017) 2(7): 11-15 Journal of Neurology
Load more

Recommended publications
  • Approach to Acute Ataxia in Childhood: Diagnosis and Evaluation Lalitha Sivaswamy, MD
    FEATURE Approach to Acute Ataxia in Childhood: Diagnosis and Evaluation Lalitha Sivaswamy, MD opsoclonus myoclonus ataxia syndrome, must receive special mention because the underlying disease process may be ame- nable to surgical intervention. In the tod- dler- and school-age groups, certain condi- tions (such as stroke and acute cerebellitis) require immediate recognition and imag- ing, whereas others (such as post-infec- tious ataxia and concussion) require close follow-up. Finally, mention must be made of diseases outside of the central nervous system that can present with ataxia, such as Guillain-Barré syndrome. he word ataxia is derived from the Greek word ataktos, which T means “lack of order.” Ataxia is characterized by disturbances in the voluntary coordination of posture and movement. In children, it is most prominent during walking (the sine qua non being a staggering gait with impaired tandem), but it can also be present during sitting or standing, or © Shutterstock when the child is performing move- Abstract Lalitha Sivaswamy, MD, is Associate Profes- ments of the arms, legs, or eyes. sor of Pediatrics and Neurology, Department Ataxia refers to motor incoordination that is This review focuses on the etiol- of Neurology, Wayne State University School of usually most prominent during movement ogy and diagnostic considerations for Medicine; and Medical Director, Headache Clinic, or when a child is attempting to maintain a acute ataxia, which for the purposes of Children’s Hospital of Michigan. sitting posture. The first part of the review this discussion refers to ataxia with a Address correspondence to: Lalitha Sivas- focuses on the anatomic localization of symptom evolution time of less than wamy, MD, Department of Neurology, Wayne ataxia — both within the nervous system 72 hours.1 State University School of Medicine, Children’s and without — using a combination of his- Motor coordination requires sensory Hospital of Michigan, 3901 Beaubien, Detroit, MI torical features and physical findings.
    [Show full text]
  • Scientific Opinion
    SCIENTIFIC OPINION ADOPTED: DD Month YEAR doi:10.2903/j.efsa.20YY.NNNN 1 Evaluation of the health risks related to the 2 presence of cyanogenic glycosides in foods other than raw 3 apricot kernels 4 5 EFSA Panel on Contaminants in the Food Chain (CONTAM), 6 Margherita Bignami, Laurent Bodin, James Kevin Chipman, Jesús del Mazo, Bettina Grasl- 7 Kraupp, Christer Hogstrand, Laurentius (Ron) Hoogenboom, Jean-Charles Leblanc, Carlo 8 Stefano Nebbia, Elsa Nielsen, Evangelia Ntzani, Annette Petersen, Salomon Sand, Dieter 9 Schrenk, Christiane Vleminckx, Heather Wallace, Diane Benford, Leon Brimer, Francesca 10 Romana Mancini, Manfred Metzler, Barbara Viviani, Andrea Altieri, Davide Arcella, Hans 11 Steinkellner and Tanja Schwerdtle 12 Abstract 13 In 2016, the EFSA CONTAM Panel published a scientific opinion on the acute health risks related to 14 the presence of cyanogenic glycosides (CNGs) in raw apricot kernels in which an acute reference dose 15 (ARfD) of 20 µg/kg bw was established for cyanide (CN). In the present opinion, the CONTAM Panel 16 concluded that this ARfD is applicable for acute effects of CN regardless the dietary source. Estimated 17 mean acute dietary exposures to cyanide from foods containing CNGs did not exceed the ARfD in any 18 age group. At the 95th percentile, the ARfD was exceeded up to about 2.5-fold in some surveys for 19 children and adolescent age groups. The main contributors to exposures were biscuits, juice or nectar 20 and pastries and cakes that could potentially contain CNGs. Taking into account the conservatism in 21 the exposure assessment and in derivation of the ARfD, it is unlikely that this estimated exceedance 22 would result in adverse effects.
    [Show full text]
  • Alcohol Sensitivity As an Endophenotype of Alcohol Use Disorder: Exploring Its Translational Utility Between Rodents and Humans
    brain sciences Review Alcohol Sensitivity as an Endophenotype of Alcohol Use Disorder: Exploring Its Translational Utility between Rodents and Humans Clarissa C. Parker 1,*, Ryan Lusk 2 and Laura M. Saba 2,* 1 Department of Psychology and Program in Neuroscience, Middlebury College, Middlebury, VT 05753, USA 2 Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; [email protected] * Correspondence: [email protected] (C.C.P.); [email protected] (L.M.S.) Received: 3 September 2020; Accepted: 9 October 2020; Published: 13 October 2020 Abstract: Alcohol use disorder (AUD) is a complex, chronic, relapsing disorder with multiple interacting genetic and environmental influences. Numerous studies have verified the influence of genetics on AUD, yet the underlying biological pathways remain unknown. One strategy to interrogate complex diseases is the use of endophenotypes, which deconstruct current diagnostic categories into component traits that may be more amenable to genetic research. In this review, we explore how an endophenotype such as sensitivity to alcohol can be used in conjunction with rodent models to provide mechanistic insights into AUD. We evaluate three alcohol sensitivity endophenotypes (stimulation, intoxication, and aversion) for their translatability across human and rodent research by examining the underlying neurobiology and its relationship to consumption and AUD. We show examples in which results gleaned from rodents are successfully integrated with information from human studies to gain insight in the genetic underpinnings of AUD and AUD-related endophenotypes. Finally, we identify areas for future translational research that could greatly expand our knowledge of the biological and molecular aspects of the transition to AUD with the broad hope of finding better ways to treat this devastating disorder.
    [Show full text]
  • Mechanisms of Ethanol-Induced Cerebellar Ataxia: Underpinnings of Neuronal Death in the Cerebellum
    International Journal of Environmental Research and Public Health Review Mechanisms of Ethanol-Induced Cerebellar Ataxia: Underpinnings of Neuronal Death in the Cerebellum Hiroshi Mitoma 1,* , Mario Manto 2,3 and Aasef G. Shaikh 4 1 Medical Education Promotion Center, Tokyo Medical University, Tokyo 160-0023, Japan 2 Unité des Ataxies Cérébelleuses, Service de Neurologie, CHU-Charleroi, 6000 Charleroi, Belgium; [email protected] 3 Service des Neurosciences, University of Mons, 7000 Mons, Belgium 4 Louis Stokes Cleveland VA Medical Center, University Hospitals Cleveland Medical Center, Cleveland, OH 44022, USA; [email protected] * Correspondence: [email protected] Abstract: Ethanol consumption remains a major concern at a world scale in terms of transient or irreversible neurological consequences, with motor, cognitive, or social consequences. Cerebellum is particularly vulnerable to ethanol, both during development and at the adult stage. In adults, chronic alcoholism elicits, in particular, cerebellar vermis atrophy, the anterior lobe of the cerebellum being highly vulnerable. Alcohol-dependent patients develop gait ataxia and lower limb postural tremor. Prenatal exposure to ethanol causes fetal alcohol spectrum disorder (FASD), characterized by permanent congenital disabilities in both motor and cognitive domains, including deficits in general intelligence, attention, executive function, language, memory, visual perception, and commu- nication/social skills. Children with FASD show volume deficits in the anterior lobules related to sensorimotor functions (Lobules I, II, IV, V, and VI), and lobules related to cognitive functions (Crus II and Lobule VIIB). Various mechanisms underlie ethanol-induced cell death, with oxidative stress and Citation: Mitoma, H.; Manto, M.; Shaikh, A.G. Mechanisms of endoplasmic reticulum (ER) stress being the main pro-apoptotic mechanisms in alcohol abuse and Ethanol-Induced Cerebellar Ataxia: FASD.
    [Show full text]
  • Management of Alcohol Use Disorders: a Pocket Reference for Primary Care Providers
    Management of alcohol use disorders: A pocket reference for primary care providers Meldon Kahan, MD Edited by Kate Hardy, MSW and Sarah Clarke, PhD Acknowledgments Mentoring, Education, and Clinical Tools for Addiction: Primary Care–Hospital Integration (META:PHI) is an ongoing initiative to improve the experience of addiction care for both patients and providers. The purpose of this initiative is to set up and implement care pathways for addiction, foster mentoring relationships between addiction physicians and other health care providers, and create and disseminate educational materials for addiction care. This pocket guide is excerpted from Safe prescribing practices for addictive medications and management of substance use disorders in primary care: A pocket reference for primary care providers, a quick-reference tool for primary care providers to assist them in implementing best practices for prescribing potentially addictive medications and managing substance use disorders in primary care, endorsed by the College of Family Physicians of Canada. This excerpt is a guide to talking to patients about their alcohol use and managing at-risk drinking and alcohol use disorders. We thank those who have given feedback on this document: Dr. Mark Ben-Aron, Dr. Peter Butt, Dr. Delmar Donald, Dr. Mike Franklyn, Dr. Melissa Holowaty, Dr. Anita Srivastava, and three anonymous CFPC reviewers. We gratefully acknowledge funding and support from the following organizations: Adopting Research to Improve Care (Health Quality Ontario & Council of Academic Hospitals of Ontario) The College of Family Physicians of Canada Toronto Central Local Health Integration Network Women’s College Hospital Version date: December 19, 2017 © 2017 Women’s College Hospital All rights reserved.
    [Show full text]
  • Ataxia Digest
    Ataxia Digest 2015 Vol. 2 News from the Johns Hopkins Ataxia Center 2016 What is Ataxia? Ataxia is typically defined as the presence of Regardless of the type of ataxia a person may have, it abnormal, uncoordinated movements. This term is is important for all individuals with ataxia to seek proper most often, but not always, used to describe a medical attention. For the vast majority of ataxias, a neurological symptom caused by dysfunction of the treatment or cure for the disease is not yet available, so cerebellum. The cerebellum is responsible for many the focus is on identifying symptoms related to or motor functions, including the coordination of caused by the ataxia. By identifying the symptoms of voluntary movements and the maintenance of balance ataxia it becomes possible to treat those symptoms and posture. through medication, physical therapy, exercise, other therapies and sometimes medications. Those with cerebellar ataxia often have an “ataxic” gait, which is walking The Johns Hopkins Ataxia Center has a that appears unsteady, uncoordinated multidisciplinary clinical team that is dedicated to and staggered. Other activities that helping those affected by ataxia. The center has trained require fine motor control like writing, specialist ranging from neurologists, nurses, reading, picking up objects, speaking rehabilitation specialists, genetic counselors, and many clearly and swallowing may be others. This edition of the Ataxia Digest will provide abnormal. Symptoms vary depending you with information on living with ataxia and the on the cause of the ataxia and are multidisciplinary center at Johns Hopkins. specific to each person. Letter from the Director Welcome to the second edition of the Ataxia Digest.
    [Show full text]
  • Medication Use and Driving Risks by Tammie Lee Demler, BS Pharm, Pharmd
    CONTINUING EDUCATION Medication Use and Driving Risks by Tammie Lee Demler, BS Pharm, PharmD pon successful completion of this ar- the influence of alcohol has Useful Websites ticle, pharmacists should be able to: long been accepted as one 1. Identify the key functional ele- of the most important causes ■ www.dot.gov/ or http://www.dot.gov/ ments that are required to ensure of traffic accidents and driv- odapc/ competent, safe driving. ing fatalities. Driving under Website of the U.S. Department of 2. Identify the side effects associated with pre- the influence of alcohol has Transportation, which contains trends Uscription, over-the-counter and herbal medi- been studied not only in ex- and law updates. It also contains an cations that can pose risks to drivers. perimental research, but also excellent search engine. 3. Describe the potential impact of certain medi- in epidemiological road side ■ www.mayoclinic.com/health/herbal- cation classes on driving competence. studies. The effort that society supplements/SA00044 4. Describe the pharmacist’s duty to warn re- has made to take serious le- Website for the Mayo Clinic, with garding medications that have the potential to gal action against those who information about herbal supplements. impair a patient’s driving competence. choose to drink and drive It offers an expert blog for further exploration about specific therapies and 5. Provide counseling points to support safe driv- has resulted in the significant to receive/share insight about personal ing in all patients who are receiving medication. deterrents of negative social driving impairment with herbal drugs. stigma and incarceration.
    [Show full text]
  • The Dentate Nucleus in Friedreich's Ataxia
    Gen_0701:Gen_0701.qxd 07 04 17 4:27 PM Page 1 Ge neratio ns The Official Publication of the National Ataxia Foundation Volume 35, Number 1 Spring 2007 The Dentate Nucleus in F riedre ich’ s Ataxia By Arnulf H. Koeppen, MD Research and Neurology Services, V. A. Medical Center, Albany, NY 12208 Friedreich’s ataxia (F RDA) affects several the small power packs that provide energy to organs, including heart, insulin-producing cells the cell in the form of adenosine triphosphate, of the pancreas, bones, peripheral nerves, spinal and the work by Dr. Lamarche and his collabo - cord, ganglia of the dorsal spinal roots, and a rators in Sherbrooke received renewed atten - specific area of the brain called the dentate tion. Indeed, the disease of the heart in FRDA nucleus. can be attributed, in some measure, to iron in Since the first description of this autosomal mitochondria. recessive ataxia by Nicholaus Friedreich in the At this time, there is no evidence that a simi - 19th century, most neurologists have consid - lar accumulation of iron occurs in the spinal ered FRDA a disease of the spinal cord. cord or its dorsal root ganglia. The normal Friedreich was aware of heart disease in his dentate nucleus of the cerebellum ( f ig. 1 on patients but thought that it was due to high page 2) contains abundant iron, possibly typhoid-like fever. making it especially vulnerable to frataxin In 1980, Dr. Jacques B. Lamarche and associ - deficiency in FRDA. The dentate nucleus is ates in Sherbrooke, Québec, Canada, discov - the main way-station for impulses leaving the ered minute iron-rich granules in heart muscle cerebellum.
    [Show full text]
  • Not to Be Disclosed to the Registrants of Hydrogen Cyanamide Formulations
    FORM HS1 Application for Reassessment of a Hazardous Substance under section 63 of the Hazardous Substances and New Organisms Act 1996 Name of Substance: Soluble concentrates containing Hydrogen Cyanamide (520 to 540 g/L) APPENDICES 2 to 11 Applicant: Chief Executive ERMA New Zealand Contents Appendix 2 – Class 1 to 8 Hazardous Properties Classification ............................................... 3 Appendix 3 - Class 9 - Hazardous Properties of Hydrogen Cyanamide and its Formulations 33 Appendix 4 - Overseas Case Studies on Human Exposure to Hydrogen Cyanamide ............. 46 Appendix 5 - NZKGI 0800 complaints for 2003 and 2004 ..................................................... 51 Appendix 6a - National Poisons Centre calls 1998-2001 ........................................................ 52 Appendix 6b - National Poisons Centre calls 2002-2005 ........................................................ 53 Appendix 7 - Toi Te Ora Public Health records of hydrogen cyanamide complaints 1998- 2004 ......................................................................................................................................... 64 Appendix 8 – Qualitative scales for describing effects ........................................................... 65 Appendix 9 – Human Health Exposure Modelling ................................................................. 68 Appendix 10 - Environmental Exposure Modelling ................................................................ 74 Application for Reassessment of Hydrogen Cyanamide: Appendices
    [Show full text]
  • Hyperemesis Gravidarum-Induced Wernicke's
    J R Coll Physicians Edinb 2009; 39:125–8 Image of the quarter © 2009 Royal College of Physicians of Edinburgh Hyperemesis gravidarum-induced CLINICAL Wernicke’s encephalopathy 1TM Anoop, 2L Rose, 3MS Sathy, 4A Kumar, 5TR Radha, 6M Thomas 1Senior Resident, Department of Medicine; 2Resident, Department of Obstetrics and Gynaecology; 3,4Senior Lecturer, Department of Obstetrics; 5Assistant Professor, Department of Medicine; 6Professor and Head of Department, Department of Obstetrics and Gynaecology, Kottayam Medical College, Kerala, India ABSTRACT Wernicke’s encephalopathy is a potentially fatal but readily reversible Published online April 2009 medical emergency caused by thiamine deficiency. A 30-year-old, 14 weeks pregnant South Indian woman presented with confusion, diplopia, blurring of Correspondence to TM Anoop, vision, gait ataxia, nystagmus and conjugate gaze palsy with a background of Department of Medicine, intractable hyperemesis gravidarum. With clinical suspicion and radiological Kottayam Medical College, Kerala, confirmation, she was diagnosed to have Wernicke’s encephalopathy. Immediate South India 686008 intervention with parenteral thiamine restored her neurological status with tel. +91 9447134973 amelioration of nystagmus, diplopia and ataxia without any neurological sequelae. e-mail [email protected] Here we report this case to illustrate the importance of early recognition of this extremely rare illness in order to avoid permanent neurological deficit. KEYWORDS Hyperemesis gravidarum, magnetic resonance imaging, Wernicke’s encephalopathy DECLaration OF INTERESTS No conflict of interests declared. CASE REPORT 100 mg daily. After two days, her neurological status improved, with amelioration of nystagmus, ataxia and A 30-year-old, 14 weeks pregnant South Indian woman diplopia. After two weeks, she was discharged with oral presented to our emergency department with confusion, thiamine 50 mg/day.
    [Show full text]
  • Acute Alcohol Intoxication May Cause Delay in Stroke Treatment
    Arokszallasi et al. BMC Neurology (2019) 19:14 https://doi.org/10.1186/s12883-019-1241-6 CASEREPORT Open Access Acute alcohol intoxication may cause delay in stroke treatment – case reports Tamas Arokszallasi1*, Eszter Balogh1, Laszlo Csiba1,2, Istvan Fekete1, Klara Fekete1 and Laszlo Olah1 Abstract Background: The signs and symptoms of acute alcohol intoxication resemble those of vertebrobasilar stroke. Due to their shared symptoms including double vision, nystagmus, dysarthria, and ataxia, the differential diagnosis of alcohol intoxication and vertebrobasilar stroke may pose a challenge. Moreover, if alcohol intoxication and stroke occur simultaneously, the signs and symptoms of stroke may be attributed to the effects of alcohol, leading to delayed stroke diagnosis and failure to perform reperfusion therapy. Case presentations: Three cases of alcohol intoxication and stroke are presented. The first patient (female, 50 years old) had dysarthria, nystagmus and trunk ataxia on admission. Her blood alcohol level was 2.3‰. The symptoms improved after forced diuresis, but 5.5 h later progression was observed, and the patient developed diplopia and dysphagia in addition to her initial symptoms. Angiography showed occlusion of the basilar artery. Intraarterial thrombolysis was performed. The second patient (male, 62 years old) developed diplopia, dysarthria and trunk ataxia after consuming 4-units of alcohol, and his symptoms were attributed to alcohol intoxication. Two hours later, neurological examination revealed dysphagia and mild right-sided hemiparesis, which questioned the causal relationship between the symptoms and alcohol consumption. Cerebral CT was negative, and intravenous thrombolysis was administered. The third patient (male, 55 years old) consumed 10 units of alcohol before falling asleep.
    [Show full text]
  • American Prohibition Year Book for 1910
    UNIVERSITY OF FLORIDA LIBRARY KtS THIS VOLUME m ^,„^ REVIEWED FOR mmwwa Or-:-- B^ pHESERVftTION DATEt |2^|i|i( " American Prohibition Year Book For 1910 Two hundred and fifty pages of the Latest Data, Tables, Diagrams, Fact and Argu- ment, Condensed for Ready Reference. ILLUSTRATED Editors CHARLES R. JONES ^^-• ^-A) ALONZO E. WILSOI^ V FRED^^Lpk^UIRES_.,.. cents P^I^^r i^nts ; Pai)ei;;\ per dozen, Cloth, 50 ; ^ ^ Vv" $2.^W^ostpaid) ' fN ^t-' Published by S. \ THE NATIONAL PROHfBKTigN PRESS 92LaSalle-Street, qiJc^slU. \ ^ \ ' » - \^:^v^ Copyright, 1910, by the National Prohibition Press, 4 General Neal Bow. Patriot, prophet, warrior, statesman, reformer; author of the Maine Law, 1851, the first state-wide prohibition statute; Prohibition candidate for Presi- dent .in 1880; born, March 20, 1804; died, October 4, 1897. " Every branch of legitimate trade has a direct pecuniary interest in the absolute suppression of the liquor traffic. Every man engaged, directly or in- directly, in the liquor trade, whether he knows it and means it or not, is an enemy to society in all its interests, and inflicts a mischief upon every in- ' dividual in it. The trade ' is an infinite evil to the country and an infinite misery to the people." 2 — — ! After Forty Years. [Written in honor of the fortieth anniversary of the National Prohi- bition movement celebrated in Chicago Sept. 24.^1909.] The faith that keeps on fighting is the one That keeps on living—yes, and growing great! The hope that sees the work yet to be done, The patience that can bid the soul to wait These three—faith, hope and patience—they have made The record of the years that swiftly sped.
    [Show full text]