DOCSLIB.ORG

Demyelinating Disease Models of Central Nervous System

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Demyelinating Disease Models of Central Nervous System Mechanisms of Immunopathology in Murine Models of Central Nervous System Demyelinating Disease This information is current as Anne M. Ercolini and Stephen D. Miller of September 29, 2021. J Immunol 2006; 176:3293-3298; ; doi: 10.4049/jimmunol.176.6.3293 http://www.jimmunol.org/content/176/6/3293 Downloaded from References This article cites 89 articles, 33 of which you can access for free at: http://www.jimmunol.org/content/176/6/3293.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 29, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2006 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. THE JOURNAL OF IMMUNOLOGY BRIEF REVIEWS Mechanisms of Immunopathology in Murine Models of Central Nervous System Demyelinating Disease1 Anne M. Ercolini and Stephen D. Miller2 Many disorders of the CNS, such as multiple sclerosis myelination reflect the diversity of clinical manifestations in (MS), are characterized by the loss of the myelin sheath humans. Although none are exact replicates of the human dis- surrounding nerve axons. MS is associated with infiltra- ease, they share many similarities and have provided insight into tion of inflammatory cells into the brain and spinal cord, the pathobiology of the human diseases they model. which may be the primary cause of demyelination or which may be induced secondary to axonal damage. Both Experimental autoimmune encephalomyelitis (EAE) the innate and adaptive arms of the immune system have EAE is a frequently studied autoimmune model of MS. EAE is Downloaded from been reported to play important roles in myelin destruc- induced in mice by active priming with whole myelin proteins tion. Numerous murine demyelinating models, both vi- or specific myelin peptide epitopes in adjuvant; the specific my- rus-induced and/or autoimmune, are available, which re- elin epitopes able to induce EAE varies with the strain of mouse used. Demyelination and paralytic episodes are associated with flect the clinical and pathological variability seen in ϩ infiltration of myelin-specific inflammatory Th1 CD4 T cells human disease. This review will discuss the immuno- http://www.jimmunol.org/ into the CNS (7). EAE can also be induced by adoptive transfer pathologic mechanisms involved in these demyelinating ϩ of myelin-specific CD4 T cells, confirming the importance of disease models. The Journal of Immunology, 2006, 176: T cells in disease induction (8). The symptoms of EAE in mice 3293–3298. are varied and mimic different clinical manifestations seen in human MS (9). Disease can be monophasic, involving an acute he axons of many vertebrate neurons are surrounded by paralytic episode followed by complete recovery; relapsing-re- a myelin sheath, which increases the speed at which the mitting, which involves multiple cycles of attack interspersed by T axon can conduct electrical impulses. Numerous in- full or partial recovery; or chronic, where disease symptoms of flammatory and metabolic disorders of the nervous system re- the initial attack either stabilize at peak levels or gradually by guest on September 29, 2021 sult in loss of the myelin sheath, with symptoms ranging from worsen over time. In the monophasic and relapse-remitting speech and visual disturbances to paralysis. Many of these dis- forms, recovery from disease is associated with clearance of in- orders are associated with immune infiltrates into the nervous flammatory infiltrates from the CNS. Susceptibility to either system, normally considered to be an immunologically privi- the monophasic or relapse-remitting subtypes has been mapped leged site. These inflammatory infiltrates may be the primary to distinct genetic loci (10). Similarly, studies suggest that these cause of the demyelination; alternatively, infiltrates may amass two MS disease subtypes are genetically distinct entities (11, 12). at sites of prior injury and contribute to progressive tissue dam- A primary hallmark of the relapsing-remitting and chronic age. Multiple sclerosis (MS) is the most prevalent human de- subtypes of EAE is the phenomenon of epitope spreading, myelinating disease of the CNS (1). The loss of myelin in MS is which is the diversification of the initial immune response, sec- thought to be autoimmune in nature because it is associated ondary to acute myelin destruction, to include reactivity to en- ϩ with elevated levels of CD4 T cells specific for the major my- dogenous CNS determinants (13). In EAE, spreading can occur elin proteins (2–4), as well as with the presence of myelin-spe- to different epitopes within the same myelin protein used to cific Abs (5, 6). initiate the disease (intramolecular spreading) or to epitopes Genetic and environmental factors (particularly exposure to within a different myelin protein (intermolecular spreading). virus or bacterial infections) are postulated to interact to varying For example, there is a sequential and hierarchical order of degrees depending on disease type to initiate autoimmune de- epitope spreading seen in the relapse-remitting disease of SJL myelination. The many described murine models of CNS de- mice primed with PLP139–151 (myelin proteolipid protein) Department of Microbiology-Immunology and Interdepartmental Immunobiology Cen- 2 Address correspondence and reprint requests to Dr. Stephen D. Miller, Department of ter, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 Microbiology-Immunology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611. E-mail address: [email protected] Received for publication November 28, 2005. Accepted for publication December 13, 2005. 3 Abbreviations used in this paper: MS, multiple sclerosis; CSF, cerebrospinal fluid; DC, dendritic cell; EAE, experimental autoimmune encephalomyelitis; HI-TMEV, Haemophi- The costs of publication of this article were defrayed in part by the payment of page charges. lus influenzae-TMEV; i.c., intracerebral; MBP, myelin basic protein; MHV, murine hep- This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. atitis virus; MOG, myelin oligodendrocyte glycoprotein; PLP, proteolipid protein; PLP, Section 1734 solely to indicate this fact. proteolipid protein; SFV, Semliki Forest virus; SV, Sindbis virus; TMEV, Theiler’s murine 1 This work was supported in part by National Institutes of Health Grants NS026543, encephalomyelitis virus; TMEV-IDD, TMEV-induced demyelinating disease. NS030871, NS023349, NS040460, and NS048411; National Multiple Sclerosis Society Research Grant RG-3489-A-6-2; and Myelin Repair Foundation Grant SM MRF-02. A.M.E. is supported by NMSS Postdoctoral Fellowship Grant FG-1596-A-1. Copyright © 2006 by The American Association of Immunologists, Inc. 0022-1767/06/$02.00 3294 BRIEF REVIEWS: IMMUNE-MEDIATED CNS DEMYELINATION ϩ ϩ (14). The first relapse is associated with Th1-type CD4 T cell APCs to Th1-type CD4 T cells (37). Proinflammatory cyto- reactivity to PLP178–191 and the second to MBP84–104 (myelin kines released by these T cells recruit monocytes and macro- basic protein). Myelin destruction during the acute disease ep- phages into the CNS, which cause damage to myelin. This sub- isode creates an inflammatory environment, leading to the in- sequent release of myelin Ags and uptake by APCs lead to the ϩ filtration of peripheral myeloid dendritic cells (DCs) to the emergence of myelin-specific CD4 T cells. Initial studies CNS, which locally present endogenously acquired myelin showed that immune responses to TMEV were detectible 5–7 ϫ epitopes to naive T cells (15). In both SJL and (SWR SJL)F1 days postinfection but that reactivity to myelin did not appear EAE models, tolerance to the primary spread epitope after in- until after the onset of clinical symptoms (30–35 days postin- duction of EAE prevented relapses and/or disease progression fection) (15, 38–40). Thus, the chronic phase of TMEV-IDD (16, 17). However, using a mouse transgenic for a single mye- is autoimmune caused by epitope spreading from viral determi- lin-specific TCRs, Jones et al. (18) showed that disease relapses nants to self-myelin determinants. Tolerance to multiple mye- could occur in the absence of reactivity to spread epitopes. lin proteins after virus infection significantly inhibits TMEV- Epitope spreading has been shown in mice double transgenic IDD, which demonstrates the importance of the myelin- for human TCR and MHC class II molecules associated with specific immune response in disease progression (41). In SJL susceptibility to MS (19, 20). The ability to clearly assess the mice, reactivity appears to multiple myelin epitopes starting role of epitope spreading in MS is hampered somewhat by the with the immunodominant epitope PLP139–151 and spreading at heterogeneity of the disease and time
Load more

Recommended publications
  • Headache in Multiple Sclerosis from a Different Perspective: a Prospective Study
    Volume 9 • Number 1 • March 2018 JOURNAL OF CLINICAL AND RESEARCHORIGINAL ARTICLEARTICLE EXPERIMENTAL INVESTIGATIONS Headache in Multiple Sclerosis from A Different Perspective: A Prospective Study Gökhan Özer¹, Ufuk Ergün², Levent Ertuğrul İnan³ 1 Sanko University Faculty of Medicine, Department of Neurology, Gaziantep, ABSTRACT Turkey Objective: It is known that patients with multiple sclerosis have a high incidence of headache. 2 Kırıkkale University School of Medicine, Kırıkkale, Turkey Although there is increasing evidence to suggest that periaqueductal gray matter (PAG) plays 3 Bozok University School of Medicine, a role in the pathophysiology of migraine headache, it is not known whether the type of Yozgat, Turkey headache may be a predictor of a MS relapse. Patients and Methods: The study enrolled 100 patients (68 females, 32 males) with clinically confirmed MS diagnosis established by McDonald diagnostic criteria. The type and duration of MS, MRI localization of lesions and cognitive status were recorded for all patients. Patients were questioned whether they experience headache during MS attacks. Results: Sixty-eight percent of the patients had headache and 32% of the patients were free of headache. Of the patients with headache, 16% had tension –type headache (TTH), 14% had migraine, 11% had primary stabbing headache (PSH), 8% had TTH+ migraine, 6% had PSH+ migraine, 6% had medication overuse headache , 2% had medication overuse headache + E-mail: [email protected] migraine, 2% had paroxysmal hemicrania, 1% had cervicogenic headache, 1% had chronic TTH, E-mail: [email protected] and 1% had unclassified headache. There was a statistically significant relationship between the E-mail: [email protected] presence of headache and MS relapse (p<0.001).
    [Show full text]
  • Development of a Central Nervous System Axonal Myelination Assay for High Throughput Screening Karen D
    Lariosa‑Willingham et al. BMC Neurosci (2016) 17:16 DOI 10.1186/s12868-016-0250-2 BMC Neuroscience METHODOLOGY ARTICLE Open Access Development of a central nervous system axonal myelination assay for high throughput screening Karen D. Lariosa‑Willingham1,2, Elen S. Rosler1,3, Jay S. Tung1, Jason C. Dugas1,4, Tassie L. Collins1,5 and Dmitri Leonoudakis1,2* Abstract Background: Regeneration of new myelin is impaired in persistent multiple sclerosis (MS) lesions, leaving neurons unable to function properly and subject to further degeneration. Current MS therapies attempt to ameliorate auto‑ immune-mediated demyelination, but none directly promote the regeneration of lost and damaged myelin of the central nervous system (CNS). Development of new drugs that stimulate remyelination has been hampered by the inability to evaluate axonal myelination in a rapid CNS culture system. Results: We established a high throughput cell-based assay to identify compounds that promote myelination. Culture methods were developed for initiating myelination in vitro using primary embryonic rat cortical cells. We developed an immunofluorescent phenotypic image analysis method to quantify the morphological alignment of myelin characteristic of the initiation of myelination. Using γ-secretase inhibitors as promoters of myelination, the optimal growth, time course and compound treatment conditions were established in a 96 well plate format. We have characterized the cortical myelination assay by evaluating the cellular composition of the cultures and expres‑ sion of markers of differentiation over the time course of the assay. We have validated the assay scalability and consist‑ ency by screening the NIH clinical collection library of 727 compounds and identified ten compounds that promote myelination.
    [Show full text]
  • Vaccination and Demyelination: Is There a Link? Examples with Anti
    Vaccination and demyelination : Is there a link? Examples with anti-hepatitis B and papillomavirus vaccines Julie Mouchet Le Moal To cite this version: Julie Mouchet Le Moal. Vaccination and demyelination : Is there a link? Examples with anti-hepatitis B and papillomavirus vaccines. Human health and pathology. Université de Bordeaux, 2019. English. NNT : 2019BORD0015. tel-02134582 HAL Id: tel-02134582 https://tel.archives-ouvertes.fr/tel-02134582 Submitted on 20 May 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. THÈSE PRÉSENTÉE POUR OBTENIR LE GRADE DE DOCTEUR DE L’UNIVERSITÉ DE BORDEAUX ÉCOLE DOCTORALE : Sociétés, Politique, Santé Publique (SP2) SPÉCIALITÉ : Pharmacologie option Pharmaco-épidémiologie, Pharmacovigilance Par Julie MOUCHET LE MOAL VACCINATION ET RISQUE DE DEMYELINISATION : EXISTE-T-IL UN LIEN ? EXEMPLES DES VACCINS ANTI-HEPATITE B ET ANTI-PAPILLOMAVIRUS Sous la direction de : Monsieur le Professeur Bernard Bégaud Soutenue publiquement le 29 Janvier 2019 Composition du jury Président : Christophe TZOURIO, Professeur des Universités
    [Show full text]
  • Multiple Sclerosis Accepted: 15 May 2016 Receiving Tysabri
    Iranian Journal Letter to Editor of Neurology Iran J Neurol 2016; 15(3): 175-176 Bacterial meningitis in a patient Received: 10 Mar 2016 with multiple sclerosis Accepted: 15 May 2016 receiving Tysabri Abdorreza Naser Moghadasi1, Soroor Advani2, Shiva Rahimi2 1 Multiple Sclerosis Research Center, Neuroscience Institute, Department of Neurology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran 2 Department of Neurology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran Keywords lesions (Figure 1-A) with no evidence of PML or Bacterial Meningitis; Multiple Sclerosis; Tysabri HSE encephalitis. Meningeal enhancement was seen after the injection of the contrast medium (Figure 1-B). The most important adverse effect of natalizumab is progressive multifocal leukoencephalopathy (PML).1 Apart from PML, there are reports of other cerebral infections including herpes simplex encephalitis (HSE)2,3 and cryptococcal meningitis4 in the literature. The patient was a 29-year-old woman, a known case of multiple sclerosis (MS) for at least 5 years. She was treated using natalizumab since 6 month before. She was under treatment with prednisolone 1 g daily for 5 days for optic neuritis, which was 2 weeks before the onset of symptoms of meningitis. Approximately three days before visiting the neurologist, a continuous headache in the left temporal lobe was developed. Figure 1. Periventricular lesions confirming the The patient was febrile at that time as well. diagnosis of multiple sclerosis (MS) in the FLAIR MRI Besides, two days before this, she had started view (A). Meningeal enhancement was seen after ciprofloxacin for treatment of a urinary gadolinium injection (B) tract infection.
    [Show full text]
  • Clinical and MRI Clues and Pitfalls in the Diagnosis and Differential Diagnosis of Multiple Sclerosis
    Clinical and MRI clues and pitfalls in the diagnosis and differential diagnosis of Multiple Sclerosis Aksel Siva, M.D. MS Clinic & Department Of Neurology Istanbul University Cerrahpaşa School of Medicine [email protected] MSParis2017 - 7th Joint ECTRIMS - ACTRIMS Meeting, 25 - 28 October 2017 Disclosure • Received research grants to my department from The Scientific and Technological Research Council Of Turkey - Health Sciences Research Grants numbers : 109S070 and 112S052.; and also unrestricted research grants from Merck-Serono and Novartis to our Clinical Neuroimmunology Unit • Honoraria or consultation fees and/or travel and registration coverage for attending several national or international congresses or symposia, from Merck Serono, Biogen Idec/Gen Pharma of Turkey, Novartis, Genzyme, Roche and Teva. • Educational presentations at programmes & symposia prepared by Excemed internationally and at national meetings and symposia sponsored by Bayer- Schering AG; Merck-Serono;. Novartis, Genzyme and Teva-Turkey; Biogen Idec/Gen Pharma of Turkey Introduction… • The incidence and prevalence rates of MS are increasing, so are the number of misdiagnosed cases as MS! • One major source of misdiagnosis is misinterpretation of nonspecific clinical and imaging findings and misapplication of MRI diagnostic criteria resulting in an overdiagnosis of MS! • The differential diagnosis of MS includes the MS spectrum and related disorders that covers subclinical & clinical MS phenotypes, MS variants and inflammatory astrocytopathies, as well as other Ab-associated atypical inflammatory-demyelinating syndromes • There are a number of systemic diseases in which either the clinical or MRI findings or both may mimic MS, which further cause confusion! Related publication *Siva A. Common Clinical and Imaging Conditions Misdiagnosed as Multiple Sclerosis.
    [Show full text]
  • October 2004
    Myelin Repair Foundation Research Progress Summary October 2004 This summary outlines progress made by the Myelin Repair Foundation research team since June 2004 and includes findings from on-going research funded by other sources that members of the team found relevant to MRF research plan. Since the success of MRF is dependent on collaboration, rather than reporting on the progress of individual projects, this report describes progress towards MRF’s overall research goals and the contributions of various team members towards completing our understanding of critical aspects of myelination and how it is affected by the multiple sclerosis (MS) disease process. 1. Fundamental control of myelination: There are several MRF investigations focused on understanding the processes that control both myelination in development and remyelination after myelin loss due to inflammation and cell death: • Dr. Ben Barres’ lab has screened thousands of genes and identified 46 genes, specific to the myelination process, that show significantly higher or lower activity levels during developmental myelination than before or after the myelination process. In addition, Dr. Barres’ lab has demonstrated the timing of these changes during the developmental myelination process. The next step is to analyze the function of each of these 46 genes by artificially controlling its level of activity (expression) and observing the effect it has on myelin formation. Finding ways to artificially manipulate the expression of each gene is a formidable task. Although the functional analysis of each gene in this group is a significant project that may take several years to complete because of the large number of genes to be analyzed, the initial identification of these active genes is providing clues to other MRF researchers that will help prioritize which genes to evaluate first and which to ignore.
    [Show full text]
  • MR Images, Brain Lesions, and Deep Learning
    applied sciences Review MR Images, Brain Lesions, and Deep Learning Darwin Castillo 1,2,3,* , Vasudevan Lakshminarayanan 2,4 and María José Rodríguez-Álvarez 3 1 Departamento de Química y Ciencias Exactas, Sección Fisicoquímica y Matemáticas, Universidad Técnica Particular de Loja, San Cayetano Alto s/n, Loja 11-01-608, Ecuador 2 Theoretical and Experimental Epistemology Lab, School of Optometry and Vision Science, University of Waterloo, Waterloo, ON N2L3G1, Canada; [email protected] 3 Instituto de Instrumentación para Imagen Molecular (i3M) Universitat Politècnica de València—Consejo Superior de Investigaciones Científicas (CSIC), E-46022 Valencia, Spain; [email protected] 4 Departments of Physics, Electrical and Computer Engineering and Systems Design Engineering, University of Waterloo, Waterloo, ON N2L3G1, Canada * Correspondence: [email protected]; Tel.: +593-07-370-1444 (ext. 3204) Featured Application: This review provides a critical review of deep/machine learning algo- rithms used in the identification of ischemic stroke and demyelinating brain diseases. It eval- uates their strengths and weaknesses when applied to real world clinical data. Abstract: Medical brain image analysis is a necessary step in computer-assisted/computer-aided diagnosis (CAD) systems. Advancements in both hardware and software in the past few years have led to improved segmentation and classification of various diseases. In the present work, we review the published literature on systems and algorithms that allow for classification, identification, and detection of white matter hyperintensities (WMHs) of brain magnetic resonance (MR) images, specifically in cases of ischemic stroke and demyelinating diseases. For the selection criteria, we used bibliometric networks. Of a total of 140 documents, we selected 38 articles that deal with the main objectives of this study.
    [Show full text]
  • Demyelination: What Is It and Why Does It Happen?
    Demyelination: What Is It and Why Does It Happen? • Causes • Symptoms • Types • MS and Demyelination • Treatment and Diagnosis • Vaccines • Takeaway What is demyelination? Nerves send and receive messages from every part of your body and process them in your brain. Nerves allow you to speak, see, feel, and think. Many nerves are coated in myelin. Myelin is an insulating material. When it’s worn away or damaged, nerves can deteriorate, causing problems in the brain and throughout the body. Damage to myelin around nerves is called demyelination. Nerves Nerves are made up of neurons. Neurons are composed of a cell body, dendrites, and an axon. The axon sends messages from one neuron to the next. The axon also connects neurons to other cells, such as muscle cells. Some axons are extremely short. Others are 3 feet long. Some axons are covered in myelin. Myelin protects the axons and helps carry axon messages as quickly as possible. Myelin Myelin is made of membrane layers that cover an axon. This is similar to the idea of an electrical wire with coating to protect the metal underneath. Myelin allows a nerve signal to travel faster. In unmyelinated neurons, a signal can travel along the nerves at about 1 meter per second. In a myelinated neuron, the signal can travel 100 meters per second. Certain diseases can damage myelin. Demyelination slows down messages sent along axons and causes the axon to deteriorate. Depending upon the location of the damage, axon loss can cause problems with feeling, moving, seeing, hearing, and thinking clearly. CAUSES Causes of demyelination Inflammation is the most common cause of myelin damage.
    [Show full text]
  • Cerebrospinal Fluid Analysis in Multiple Sclerosis Diagnosis: an Update
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Archivio istituzionale della ricerca - Università di Palermo medicina Review Cerebrospinal Fluid Analysis in Multiple Sclerosis Diagnosis: An Update Bruna Lo Sasso 1, Luisa Agnello 1, Giulia Bivona 1 , Chiara Bellia 1 and Marcello Ciaccio 1,2,* 1 Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90100 Palermo, Italy; [email protected] (B.L.S.); [email protected] (L.A.); [email protected] (G.B.); [email protected] (C.B.) 2 Department Laboratory Medicine, University-Hospital, 90100 Palermo, Italy * Correspondence: [email protected]; Tel.: +39-091-23865701; Fax: +39-091-655-3275 Received: 25 March 2019; Accepted: 30 May 2019; Published: 4 June 2019 Abstract: Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS) with brain neurodegeneration. MS patients present heterogeneous clinical manifestations in which both genetic and environmental factors are involved. The diagnosis is very complex due to the high heterogeneity of the pathophysiology of the disease. The diagnostic criteria have been modified several times over the years. Basically, they include clinical symptoms, presence of typical lesions detected by magnetic resonance imaging (MRI), and laboratory findings. The analysis of cerebrospinal fluid (CSF) allows an evaluation of inflammatory processes circumscribed to the CNS and reflects changes in the immunological pattern due to the progression of the pathology, being fundamental in the diagnosis and monitoring of MS. The detection of the oligoclonal bands (OCBs) in both CSF and serum is recognized as the “gold standard” for laboratory diagnosis of MS, though presents analytical limitations.
    [Show full text]
  • Acute Disseminated Encephalomyelitis Or Multiple Sclerosis: Can the Initial Presentation Help in Establishing a Correct Diagnosi
    636 REVIEW Acute disseminated encephalomyelitis or multiple sclerosis: can the initial presentation help in establishing a correct Arch Dis Child: first published as on 20 May 2005. Downloaded from diagnosis? R C Dale, J A Branson ............................................................................................................................... Arch Dis Child 2005;90:636–639. doi: 10.1136/adc.2004.062935 The differential diagnosis of CNS white matter disease is and MS cases must manifest disseminated disease of the CNS (more than one clinical or broad, and can be divided into vascular, metabolic, radiological site). Diseases isolated to specific infective, or inflammatory aetiologies. Isolated areas of the CNS (isolated optic neuritis, trans- inflammatory disorders of the CNS are often associated verse myelitis, and brain stem dysfunction) are considered distinct from both ADEM and MS with demyelination, and the two terms (inflammatory and (clinically and prognostically), and will not be demyelinating) are often used in conjunction. When the discussed in this review.89 disease is monophasic, the term acute disseminated 1 DEMOGRAPHICS encephalomyelitis (ADEM) is used. ADEM typically occurs Monophasic ADEM is more common in children, as a post-infectious phenomenon, and by definition, must whereas MS is more common in adults. Between be an isolated (monophasic) episode. If a relapse occurs 2.7% and 4.4% of MS presentations occur in children less than 16 years of age.8 Mikaeloff et al shortly after the ADEM presentation in association with a showed a mean age of 7.1 years and 12.0 years in further infection or steroid withdrawal, the term MDEM paediatric ADEM and MS patients respectively.8 (multiphasic disseminated encephalomyelitis) is used.
    [Show full text]
  • A Case of Balo's Concentric Sclerosis with Typical MRI Findings and Complete Resolution of the Lesion Followi
    A Case of Balo’s Concentric Sclerosis with Typical MRI Findings and Complete Resolution of the Lesion Following Treatment Shitiz K Sriwastava, M.D, Aaron Desai, M.D, Evanthia Bernitsas, MD Department of Neurology, Wayne State University School of Medicine, Detroit, MI INTRODUCTION PATEINT’S CLINCIAL HISTORY RESULTS Balo’s Concentric Sclerosis (BCS) is a rare and severe A year later, following an MS relapse, repeat MRI scan of the After treatment with steroids and plasma exchange, the demyelinating disease of the central nervous system (CNS), brain showed a small enhancing focus at the posterior level of patient’s disease course has been benign with only residual left and it is often viewed as a variant of multiple sclerosis (MS). the Sylvian fissure on the right side, otherwise it was hemiparesis and total resolution of the original Balo‐like lesion. unchanged. The typical lesion in BCS is characterized by concentric layers of demyelination alternating with layers of preserved myelin A follow‐up MRI scan showed total resolution of the original Three years later, the patient experienced a severe relapse and is known as the “onion bulb” appearance. BCS lesion. with new left‐sided weakness and hemiparetic gait. MRI scan It was thought that BCS represents an aggressive MS variant showed classic BCS appearance with alternating hypo and with poor prognosis. hyperintense rings. The patient was treated with IV DISCUSSION However, recent literature contradicts prior observations. We methylprednisolone with some improvement, followed by 6 present a case of BCS with typical MRI findings and complete sessions of plasmapheresis. We present this case of BCS to shed light on this rare subtype resolution of the lesion following treatment.
    [Show full text]
  • Updated Criteria for Diagnosing Multiple Sclerosis
    r e v i e w a r t i c l e Updated criteria for diagnosing Multiple Sclerosis or in the case of progressive MS, a slow or step- Key take home messages wise progression of disability over a period of • The diagnostic criteria for MS have at least six months been recently updated • and objective clinical evidence of lesions in • These criteria should only be applied two or more distinct sites in the white matter to populations in whom MS is of the central nervous system common and patients who present • with no more satisfactory explanation. Peter Brex with typical symptoms for which no The Schumacher criteria were purely clinical, MB BS, MD, FRCP is a Consultant Neurologist at King’s College Hospital better explanation can be found although investigations were encouraged (blood, NHS Foundation Trust. He trained in • All patients with suspected MS should urine, chest X-ray, CSF analysis) to exclude London and was appointed to his current have an MRI brain scan; spinal cord alternative conditions. role in 2005. He specialises in multiple imaging is not mandatory Over the next few years modifications to the sclerosis, with a particular interest in early 2,3 prognostic markers and the management • Unmatched oligoclonal bands in the Schumacher criteria were published but in 1983 of MS during pregnancy. CSF can be used as a substitute for the Schumacher criteria were replaced by criteria demonstrating dissemination in time, developed by a committee chaired by Charles allowing an earlier diagnosis than was Poser (1923 – 2010).4 The Poser criteria incorpor- previously possible ated laboratory and clinical tests developed in the previous decade to support the diagnosis with ‘paraclinical evidence’ of lesions.
    [Show full text]