DOCSLIB.ORG

Magnetization Transfer Imaging to Investigate Tissue Structure and Optimise Detection of Blood Brain Barrier Leakage in Multiple Sclerosis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Magnetization Transfer Imaging to Investigate Tissue Structure and Optimise Detection of Blood Brain Barrier Leakage in Multiple Sclerosis Magnetization Transfer Imaging to Investigate Tissue Structure and Optimise Detection of Blood Brain Barrier Leakage in Multiple Sclerosis Dr Nicholas Charles Silver, MBBS; MRCP A thesis submitted to the University of London for the degree of Doctor of Philosophy March 2001 NMR Research Unit Institute of Neurology University College London Queen Square London WCIN 3BG United Kingdom ProQuest Number: U643048 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest U643048 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 Abstract Magnetic resonance imaging (MRI) has become a powerful researeh tool for in vivo evaluation and monitoring of multiple sclerosis (MS). Conventional MRI techniques detect changes in the density or relaxation characteristies of “free” water protons. They are sensitive but lack pathological specificity. Magnetization transfer (MX) imaging provides a method for evaluating those protons “bound” to maeromolecular struetures. Part one of this thesis outlines the clinical and pathological features of MS and discusses the importance of demyelination and blood-brain barrier breakdown. An introduction to MRI and MX imaging techniques is provided. Issues related to quality assuranee and standardization for MX imaging are explored. In part two, MX ratio (MXR) is explored as a putative quantitative marker of demyelination and associated tissue destruetion. In part three, MX contrast (MXC) is explored as a novel mechanism for improving the detection of focal contrast-enhancing lesions. A normative database for MXR in healthy white matter is presented in ehapter four. Highest values are found where myelin density is greatest. Minor age-related MXR reduction is observed. In ehapter five, MXR is evaluated in central pontine myelinolysis, a rare neurological condition characterised pathologieally by severe demyelination. The results support myelin as the predominant contributor to MXR values in white matter. In ehapter six, MXR is employed as a putative marker of demyelination to explore the relationships between demyelination and blood-brain barrier damage in acute MS lesions. New techniques for registering two-dimensional images were implemented to allow reliable measurement of MXR prior to visible lesion formation. No evidence was found to suggest signifieant demyelination prior to opening of the blood-brain barrier. Chapter seven details the novel application of MXR measurement in the cervieal spinal eord and preliminary data are presented showing reduction in MS. Further studies in this clinically eloquent region will be of interest. The potential for MXC to improve gadolinium enhancing lesion deteetion in MS is explored in the ehapters eight and nine. First, a cross-seetional study explores how the detection of enhancing lesions may be improved by MXC; in conjunction with a triple-dose gadolinium and subsequent delay prior to imaging, sensitivity was more than doubled. Xriple-dose improved sensitivity more than MXC. Finally, a serial study is presented that confirms a significant increase in longitudinal sensitivity for such techniques. The potential benefits for monitoring phase II exploratory treatment trials in MS are evaluated. Acknowledgements Thanks to my supervisor David Miller for his guidance and unfailing support throughout my time in research. I have benefited from both his global vision and attention to detail. I would especially like to thank Ian McDonald for his clarity, wisdom and kindness, all of which have provided a continued source of inspiration. Thanks also to Alan Thompson for his input. Many thanks to Paul Tofts and Gareth Barker for their theoretical and practical input. I am indebted to Tina Good for her radiological expertise, enthusiasm, and friendship. Thanks also to Ivan Moseley and Mary Gawne-Caine. I have enjoyed the international collaboration afforded by MAGNIMS and would particularly like to thank Achim Gass and Wolfgang Schreiber for their helpful suggestions and Massimo Fillipi and Maria Pia Sormani for their collaboration. I am grateful to Mark Symms for his genuine enthusiasm and novel ideas. This thesis would not have been possible without the dedication and hard work of all of the radiographers in the unit. Special thanks to Dave MacManus and also to Alison Fletcher, Beth Gunn, and Andrew Howe. Thanks to my fellow “Moorfields Clinic” colleagues who provided invaluable “out of hours”advice. In particular, thanks to Gavin Giovannoni for his collaboration and inspiration, John Mottershead for his companionship and laboratory “cookery” skills (not forgetting the help from Alison Green and Geoff Keir), Bob Brenner, Nick Losseff (for imparting his statistical and software knowledge and for showing how the best ideas are the simple ones), Ming Lai (for letting me use his data), Charlie Davie, Jonathon O’Riordan and Katia Cikurel. I particularly wish to thank my friends and fellow members of the NMR Unit, including Michael Sailer, Tina Holmes, Val Stevenson, Niall Tubridy, David Werring, Siobhan Leary, Paul Molyneux, Peter Brex, Chris Clark, Jackie Foong, Collette Griffin, Arun Reginald and Geoff Parker. My thanks to you all for your kinship and support through the good times and the bad. Special thanks to my successor, Tony Traboulsee, for proof reading this tome. Thanks also to my non-medical friends, Lany, Moss, Lou, and Jonny for their much appreciated diversions. Thanks to Di for her unfailing support, enthusiasm, and understanding (thank you also for providing me with the most wonderful distractions ever imagined, Amy and Ben). Thank you also to my parents, Trevor and Jill, for their constant encouragement and faith in me. A special thanks to the Multiple Sclerosis Society of Great Britain and Northern Ireland for their generous support throughout my research studentship. Finally, thank you everyone who volunteered to be studied - my heartfelt gratitude to you all for your unerring dedication. Statement of Authorship All projects outlined in this thesis represent my original and personal work. This thesis would not however have been possible without specific individual contributions from collaborators within the NMR Unit and other research centres. With the following exceptions and those listed in the text of this thesis, I was responsible for the initiation and design of all project protocols, recruitment of subjects for study, acquisition of all clinical and radiological data (with help from the individual radiographers who performed all scanning), analysis of all image data, statistical testing, and interpretation of the subsequent results: In Chapter 3, Drs. John Mottershead, Geoff Keir, and Alison Green helped design and manufacture the MTR phantoms. In Chapter 5, Dr Charlie Davie acquired the proton MRS control data from four healthy volunteers. In Chapter 6, Dr Ming Lai recruited and acquired data from three of the subjects. In Chapter 9, Dr Maria Pia Sormani performed the sample size calculations in conjunction with Dr Massimo Filippi. To Diane Table of Contents Page Abstract 2 Acknowledgements 3 Statement of Authorship 4 Dedication 5 Table of Contents 6 List of Figures 11 List of Tables 15 List of Abbreviations 17 List of Publications 18 PART ONE BACKGROUND 1. Introduction 1.1 Personal and social cost implications of multiple sclerosis 21 1.2 Background 22 1.3 Aims 24 1.4 Multiple sclerosis 1.4.1 Clinical background and definitions 25 1.4.2 Diagnosis 25 1.4.3 Clinical manifestations 33 1.4.4 Aetiology 36 1.4.5 Neuropathology 38 1.4.6 Treatment - disease modification 49 1.4.7 Treatment - symptomatic strategies 52 and rehabilitation 1.5 MRI to monitor putative therapies in multiple sclerosis 54 2. Common Methodology 2.1 Introduction 56 2.2 Basic principles of magnetic resonance imaging 2.2.1 Introduction 56 2.2.2 Quantum mechanical description 57 o f magnetic resonance 2.2.3 Classical description of magnetic resonance 59 2.2.4 Factors affecting the NMR signal: 63 Spin-lattice and spin-spin relaxation 2.2.5 Free induction decay and signal detection 66 2.2.6 Spin echoes 67 2.2.7 Relaxation mechanisms 70 2.2.8 Tissue NMR relaxation properties 74 2.2.9 Obtaining spatial information with 76 magnetic resonance imaging 2.2.10 MRIinstrumentation 80 2.2.11 Alternative pulse sequences for imaging 81 2.3 Magnetization Transfer: principles and techniques 2.3.1 Introduction 83 2.3.2 Basic principles of magnetization transfer 84 2.3.3 Saturation transfer 85 2.3.4 Magnetization transfer in biological tissue 87 2.3.5 Preliminary in vivo demonstration of MT 90 effects in biological tissue 2.3.6 In vivo applications of magnetization 91 transfer imaging 2.4 MRI to assess blood-brain barrier integrity 2.4.1 The blood-brain barrier 96 2.4.2 Contrast agents for MRI 97 2.4.3 Pharmacokinetics of gadopentate dimeglumine 101 2.4.4 Safety and tolerance of gadopentate dimeglumine 101 2.4.5 Sensitivity of contrast-enhanced MRI 103 2.5 MRI postprocessing to quantify pathological change 2.5.1 Qualitative MRI 104 2.5.2 Quantitative M RI 105 2.6 Clinical measurement
Load more

Recommended publications
  • 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]
  • And Multiple Sclerosis Particular Problem, I Wish to Make the Follow
    524 Maters arising prolong the lives of those suffering, thereby Most of these problems are not taken into 6 Poser C, Paty D, Scheinberg L, et al. New J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.55.6.524-b on 1 June 1992. Downloaded from providing the necessity for self-action by the consideration in Sibley's article. diagnostic criteria for multiple sclerosis. Ann patient. It is germane to point out that the "scien- Neurol 1983;13:227-31. Perhaps when we advise patients and tific" evidence of epidemiology and biostatis- families who face difficult decisions, we tics overlooks the fact that such studies can at Sibley et al reply: would be better to heed the available evi- best only be estimates within a cohort and dence about who will do well and who will do cannot be generalised; epidemiological stud- We age- and sex-matched MS patients with badly rather than withholding recommenda- ies are most useful in providing aetiological healthy controls solely to establish the degree tions because unduly cautious statisticians clues but cannot be used to deny possible of accident-proneness of MS patients. It choose to neglect the downside effects of causal relationships.2 As was pointed out by probably needs to be clearly restated that the their theoretical arguments. Neurologists are Schoenberg, "Statistical significance (or lack patients were used as their own controls in an especially favourable position to under- thereof) does not equal biological when they were not "at risk". stand the misery that accompanies chronic, significance". Physical trauma had no positive influence overwhelming brain damage.
    [Show full text]
  • (Pre-Allison & Millar) Ipsen Criteria: 1939-48, Boston, MA
    Early criteria (pre-Allison & Millar) Ipsen criteria: 1939-48, Boston, MA USA1 - Probable MS o Those cases with records presenting convincing evidence - Possible MS o Those cases whose evidence was more doubtful. Ipsen acknowledges these allocations are fairly arbitrary but also notes that absolutely certainty of diagnosis is impossible except by autopsy, a limitation we are similarly affected by even today. Westlund & Kurland: 1951, Winnipeg, MT Canada & New Orleans, LA USA2 Diagnostic groupings as follows, with no explicit requirements for each, rather deferring to the discretion of the examining neurologist: - Certain MS - Probable MS - Possible MS o In this class, the changes for and against MS were considered approximately even - Doubtful, unlikely or definitely-not MS2 Sutherland criteria: 1954, Northern Scotland3 - Probable MS o This category for patients in whom the history, the results of clinical examination and, where available, hospital investigations, indicated that the diagnosis of MS was beyond reasonable doubt. - Possible MS o Patients in whom a diagnosis of MS appears justifiable but in which the diagnosis could not be established beyond reasonable doubt; o This group also included patients who did not wish to be examined or could not be seen – review of hospital records for these patients suggested a diagnosis of MS - Rejected cases o Patients found to be suffering from a disease other than MS Allison & Millar Criteria and variants Allison & Millar criteria: 1954, Northern Ireland4 - Early disseminated sclerosis: 1) this category for patients with little in the way of symptomatic presentation but with a recent history consistent with disease onset, i.e. optic neuritis, ophthalmoplegia (double vision), vertigo, sensory problems like pins & needles or numbness, or motor problems like weakness.
    [Show full text]
  • Nayakphd2018.Pdf
    This work is protected by copyright and other intellectual property rights and duplication or sale of all or part is not permitted, except that material may be duplicated by you for research, private study, criticism/review or educational purposes. Electronic or print copies are for your own personal, non- commercial use and shall not be passed to any other individual. No quotation may be published without proper acknowledgement. For any other use, or to quote extensively from the work, permission must be obtained from the copyright holder/s. 1 2 3 Structure and function of the visual pathway in demyelinating optic neuropathy Devaki Nayak Thesis submitted for degree of PhD June 2018 Keele University 4 Acknowledgments I take this opportunity to thank Professor Hawkins for all the help and advice that he provided me over the entire duration of work. I would like to thank the team at Keele Multiple Sclerosis Research Group for their help, friendship and humor throughout the period of research. I once again thank Professor Hawkins for guiding an Ophthalmologist to explore the world of MS in Neurology. I would like to thank Professor Peter Jones for his valuable input on statistical methodology and Professor Richard Strange for his weekly input on statistics from the very first recruitment into this project. I specially want to thank Dr. Ramachandran who spent considerable amount of time in guiding the project and helping with meetings with Professor Jones. I am also thankful to Janice Guildford who helped me with knowledge of existent database in the Keele Multiple Sclerosis Research Group.
    [Show full text]
  • Recommended Standard of Cerebrospinal Fluid Analysis in the Diagnosis of Multiple Sclerosis a Consensus Statement
    NEUROLOGICAL REVIEW Recommended Standard of Cerebrospinal Fluid Analysis in the Diagnosis of Multiple Sclerosis A Consensus Statement Mark S. Freedman, MSc, MD, FRCPC; Edward J. Thompson, DSc; Florian Deisenhammer, MD; Gavin Giovannoni, PhD; Guy Grimsley, PhD; Geoffrey Keir, PhD; Sten Öhman, PhD; Michael K. Racke, MD; Mohammad Sharief, PhD; Christian J. M. Sindic, MD, PhD; Finn Sellebjerg, MD, PhD, DMSci; Wallace W. Tourtellotte, MD, PhD ew criteria for the diagnosis of multiple sclerosis (MS) were published as the result of an internationally formed committee. To increase the specificity of diagnosis and to minimize the number of false diagnoses, the committee recommended the use of both clinical and paraclinical criteria, the latter involving information obtained from Nmagnetic resonance imaging, evoked potentials, and cerebrospinal fluid (CSF) analysis. Although rigorous magnetic resonance imaging requirements were provided, the “new criteria paper” fell short in terms of guidelines as to how the CSF analysis should be performed and simply equated the IgG index with isoelectric focusing, without any justification. The spectrum of parameters ana- lyzed and methods for CSF analysis differ worldwide and often yield variable results in terms of sensitivity, specificity, accuracy, and reliability, with no decided “optimal” CSF test for the diag- nosis of MS. To address this question specifically, an international panel of experts in MS and CSF diagnostic techniques was convened and the result was this article, representing a consensus of all the participants. These recommendations for establishing a standard for the evaluation of CSF in patients suspected of having MS should greatly complement the new criteria in ensuring that a correct diagnosis of MS is being made.
    [Show full text]
  • New Diagnostic Criteria for Multiple Sclerosis: Guidelines for Research Protocols
    SPECIAL ARTICLE New Diagnostic Criteria for Multiple Sclerosis: Guidelines for Research Protocols Charles M. Poser, MD,l Donald W. Paty, MD,’ Labe Scheinberg, MD,3 W. Ian McDonald, FRCP,4 Floyd A. Davis, MD,’ George C. Ebers, MD,‘ Kenneth P. Johnson, MD,’ William A. Sibley, MD,8 Donald H. Silberberg, MD,9 and Wallace W. Tourtellotte, MD” Several schemes for the diagnosis and clinical clas- Method and Procedure sification of multiple sclerosis (MS) have been ad- On April 26 and 27, 1982, the following persons participated vanced [l}. The best known is that published by in a Workshop on the Diagnosis of Multiple Sclerosis, held in Schumacher et alC31. The criteria for this scheme were Washington, DC, for the purpose of establishing new diag- established in order to select patients for participation nostic criteria for MS: Bruce Becker (National Naval Medical in therapeutic trials, and pertain only to what might be Center),Jerry Blaivas (Columbia), Keith Chiappa (Harvard), called definite MS. No provision was made for incor- Floyd Davis (Rush), Burton Drayer (Duke), George Ebers porating supportive laboratory data into the diagnostic (Western Ontario), Andrew Eism (British Columbia), criteria. Robert Herndon (Rochester, NY), Kenneth Johnson (Mary- As no reliable specific laboratory test for the diag- land), Ian McDonald (National Hospital, London), Dale nosis of MS has been discovered, the diagnosis remains McFarlin (NINCDS), Donald Paty, Co-chairman (British a clinical one, and there is still a need for clinical diag- Columbia),Janis Peyser
    [Show full text]
  • Swedish Neuroscience Institute
    Diagnosing MS MS can be difficult to diagnose. There is no test that is 100% certain in identifying who has the disease and who does not have the disease. This has led to the development of several sets of diagnostic criteria over the years. One of the first sets of criteria was known as the Schumacher criteria. These criteria required dissemination in both space and time, meaning that patients had to have more than one part of the nervous system involved (dissemination in space) at more than one time (dissemination in time). Dissemination is space and time is still a cornerstone of the diagnosis. The Schumacher criteria were followed by the Poser Criteria which included testing for spinal fluid and recognized degrees of certainty with the diagnosis. The best and most current set of criteria for diagnosing MS is the McDonald criteria. These were first developed in 2001 by an international panel in association with the National MS Society. The McDonald criteria were revised in 2005 and again in 2010. The 2010 revision to the McDonald criteria is the current standard for diagnosis. Overview The primary goal of the McDonald Criteria is to enable the diagnosis of MS sooner and to permit earlier treatment of MS. For clinical research trials it is important to ensure that those without a definite diagnosis of MS are not enrolled. The bottom line is that there have to be 2 attacks in time and at 2 locations. You can get the locations in time either by clinical attacks or by MRI changes over time.
    [Show full text]
  • MS Misdiagnosis— an Analysis from Case Studies
    6/6/2011 MS Misdiagnosis— An Analysis From Case Studies Joseph R. Berger, MD Ruth L. Works Professor and Chairman Department of Neurology University of Kentucky College of Medicine Chief of Department and Head of MS Center University of Kentucky Medical Center Lexington, Kentucky Disclosures Sources of Funding for Research: Bayer HealthCare Pharmaceuticals; Biogen Idec; EMD Serono, Inc. Consulting Agreements: Bayer HealthCare Pharmaceuticals; Biogen Idec; Genentech, Inc.; GlaxoSmithKline; Millennium Pharmaceuticals,,; Inc.; Perseid Other support: Bayer HealthCare Pharmaceuticals; Biogen Idec; Serono, Inc. Financial Interests/Stock Ownership: None Discussion of Off-Label, Investigational, or Experimental Drug Use: Cyclophosphamide, intravenous immunoglobulins A handful of patience is worth more than a barrel full of brains. Dutch Proverb 1 6/6/2011 Causes of Misdiagnosis • Diagnosis momentum • Diagnosis even on insufficient evidence becomes fixed in a doctor’s mind • Framing effects • Being swayed by subtle wording or focusing on certain aspects of a case more than others • Satisfaction of search • Stopping when you find a satisfying diagnosis • Confirmation bias (anchoring) • Dismissing material that does not fit with your diagnostic impression • Attribution error • Failing to consider a diagnosis that does not fit the prototype • Representativeness error • Failing to consider possibilities that contradict the prototype and base rate of disease • Failing to account for base rates (“If you hear hoof beats, think horses, not zebras”) •
    [Show full text]
  • Multiple Sclerosis Disease Modifying Therapies Update
    Practical Controversies in MS Lucas McCarthy, MD, MSc Neurologist, Director MS Center Practical Controversies How to approach common questions in the gray-zone of evidence- based practice? © 2016 Virginia Mason Medical Center The Evidence Free Zone © 2016 Virginia Mason Medical Center Practical Controversies in MS • Misdiagnosis of MS • Vitamin D testing / supplementation • Use of complimentary / experimental treatments • Treatment of Progressive MS © 2016 Virginia Mason Medical Center Poll Everywhere – Audience Participation Open cell phone or laptop to following link to participate in live questions https://pollev.com/MSsummit © 2016 Virginia Mason Medical Center Misdiagnosis of Multiple Sclerosis Misdiagnosis of MS Updated 2017 McDonald MS Diagnostic Criteria Easier to diagnosis = Easier to misdiagnose? © 2016 Virginia Mason Medical Center MS Diagnosis – 2017 Updated Criteria Lesions: ≥ 2 characteristic lesions (>3mm) in ≥ 2 different locations Symptoms: objective clinical evidence of at least 1 lesion Relapse: ≥ 1 characteristic clinical attack Changes over Time: ≥2 CSF Oligoclonal bands or >1 attack over time or new lesions over time (including enhancing and non-enhancing) *No other reasonable diagnosis © 2016 Virginia Mason Medical Center MS Diagnosis – Evolving Diagnostic Criteria MS Diagnostic Criteria Comments 1965 - Schumacher Criteria 2 attacks of neurologic symptoms > 24 hours in duration, separated by at least one month. No MRI yet 1983 - Poser Criteria Added cerebrospinal fluid (CSF) markers and Evoked Potentials to diagnostic
    [Show full text]
  • Prevalence of Multiple Sclerosis in Al Quseir City, Red Sea Governorate, Egypt
    Journal name: Neuropsychiatric Disease and Treatment Article Designation: Original Research Year: 2016 Volume: 12 Neuropsychiatric Disease and Treatment Dovepress Running head verso: El-Tallawy et al Running head recto: Epidemiology of multiple sclerosis in Egypt open access to scientific and medical research DOI: http://dx.doi.org/10.2147/NDT.S87348 Open Access Full Text Article ORIGINAL RESEARCH Prevalence of multiple sclerosis in Al Quseir city, Red Sea Governorate, Egypt Hamdy N El-Tallawy1 Background: Multiple sclerosis (MS) is a chronic and disabling disorder with considerable Wafaa M A Farghaly1 social effects and economic sequelae. It is one of the major causes of disability in young Reda Badry1 adults. Nabil A Metwally2 Objectives: This study aimed at detecting the prevalence of MS among the population of Ghaydaa A Shehata1 Al Quseir city. Tarek A Rageh1 Methods: This study is a part of door-to-door survey of major neurological disorders that was conducted in Al Quseir city, Red Sea Governorate, Egypt. The sample size was 33,285 persons. Mohamed Abd El Hamed1 The youngest patient was 17 years old. The number of people at and above 17 years of age Mahmoud R Kandil1 was 21,827. They were screened by three neurologists. Then, the positive cases were subjected 1Department of Neurology and to meticulous clinical evaluation by three staff members of Department of Neurology, Assiut Psychiatry, Assiut University Hospital, Assiut, Egypt; 2Department of University Hospital, Egypt. Essential investigations were done. For personal use only. Neurology and Psychiatry, Al Azhar Results: A total of three cases of MS were diagnosed with an age-specific prevalence $17 University Hospital, Assiut Branch, years of 13.7/100,000.
    [Show full text]
  • The Diagnosis of Multiple Sclerosis
    TheThe DiagnosisDiagnosis OfOf MultipleMultiple SclerosisSclerosis DRDR SAHERSAHER HASHEMHASHEM PROFPROF OFOF NEUROLOGYNEUROLOGY CAIROCAIRO UNIVERSITYUNIVERSITY ThereThere isis nono pathpath gnomonicgnomonic oror perfectperfect laboratorylaboratory testtest whichwhich maymay bebe usedused inin isolationisolation toto reliablyreliably diagnosediagnose MS.MS. TheThe keykey toto correctcorrect diagnosisdiagnosis isis typicalitytypicality TheThe duckduck testtest isis importantimportant ,, (( isis thisthis aa duck,duck, itit lookslooks likelike aa duck,duck, walkwalk likelike andand quacksquacks likelike aa duck,duck, thenthen itit isis probablyprobably aa duck.duck. duck, and QuestionQuestion OneOne WhatWhat isis thethe mostmost commoncommon mistakemistake duringduring MSMS diagnosis?diagnosis? TheThe mostmost commoncommon mistakemistake duringduring MSMS diagnosisdiagnosis isis aa falsefalse positivepositive attributionattribution thatthat isis makingmaking aa diagnosisdiagnosis ofof MSMS inin patientspatients whowho dondon ’’tt havehave MS.OftenMS.Often thisthis errorerror isis thethe resultresult ofof uncriticaluncritical oror causalcausal reliancereliance onon MRIMRI withoutwithout appropriateappropriate clinicalclinical correlationcorrelation 6262 patientspatients assessedassessed byby generalgeneral neurologistsneurologists andand reassessedreassessed byby otherother generalgeneral neurologistsneurologists usingusing McMc DonaldDonald ’’ss criteriacriteria andand foundfound 51%51% ofof MSMS patientspatients werewere notnot confirmed.confirmed.
    [Show full text]
  • THE DIAGNOSIS of MULTIPLE SCLEROSIS C B Tan
    C LEADING ARTICLE j THE DIAGNOSIS OF MULTIPLE SCLEROSIS C B Tan SINGAPORE MED J 1992; Vol 33: 561-562 Demyelinating diseases in adults, in which the pathology is tomatic dissemination in space or detect evidence of inflam- in the white matter predominantly of the central nervous sys- mation in the central nervous system are useful aids in the tem, are caused by a variety of viral infections and anoxic - diagnosis of MS. The risk of developing MS following an toxic conditions"). However, the most common primary isolated acute syndrome of brainstem or spinal cord is much demyelinating disease is multiple sclerosis (MS) which is char- higher in patients with disseminated lesions on MRI and in acterised by multifocal inflammatory demyelination in the cen- those with positive oligoclonal band1"). Similarly, the risk of nervous tral system and recognised by its relapsing and remit- developing MS in isolated optic neuritis may be higher in ting character. As there are no pathognomonic laboratory tests, patients who have abnormal white matter lesions on MRIOt). the diagnosis has always been a clinical one. Diagnostic crite- The existing diagnostic criteria for MS were revised at a Work- ria have continued to evolve since its delineation as a disease shop on the Diagnosis of Multiple Sclerosis in 1982 whereby entity by Charcot more than a century ago. The disease typi- paraclinical findings were incorporated for the purpose of ex- young cally occurs in women of northern European Caucasian tending the limits of the diagnostic criteria thus making a larger descent in temperate countries1). The prevalence of the disease reservoir of patients for investigative purposes101.
    [Show full text]