DOCSLIB.ORG

A Histopathological and Magnetic Resonance Imaging Assessment of Myelocortical Multiple Sclerosis: a New Pathological Variant

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Histopathological and Magnetic Resonance Imaging Assessment of Myelocortical Multiple Sclerosis: a New Pathological Variant A HISTOPATHOLOGICAL AND MAGNETIC RESONANCE IMAGING ASSESSMENT OF MYELOCORTICAL MULTIPLE SCLEROSIS: A NEW PATHOLOGICAL VARIANT A dissertation submitted to Kent State University in partial fulfillment of the requirements for the degree of Doctor of Philosophy By: Megan C. Vignos May, 2016 © Copyright All rights reserved Table of Contents Table of Contents……………………………………………………………………………...ii List of Figures………………………………………………………………………………....iv List of Tables…………………………………………………………………………………..v Acknowledgements……………………………………………………………………………vi Chapters I. Introduction…………………………………………………………………....1 II. Multiple Sclerosis: General Background ………………………………...…...6 Diagnosis Criteria of MS……………………………………………………...6 Evaluating Neurological Disability……………………………………………9 Magnetic Resonance Imaging in MS Diagnosis……………………………...10 Clinical Manifestations………………………………………………………..12 MS Pathology………………………………………………………………....20 Magnetic Resonance Imaging Metrics Related to MS Pathology………….…30 Disease-Modifying Therapies for MS…………………………………….…..52 Conclusion of Review…………………………………………………….…..58 Research Questions and Hypotheses…………………………………….……59 III. Patients and Methods…………………………………………………..……...63 Subjects………………………………………………………………….…….63 Postmortem Tissue Processing……………………………………………..….67 Quantification of Macroscopic Cerebral White Matter Lesions…………….....68 Region Selection…………………………………………………………….…69 MRI Procedures……………………………………………………………..…69 Immunohistochemical Analysis………………………………………….……72 Tissue Processing and Paraffin Embedding of Hemispheric Sections………...73 Quantification of Histology…………………………………………………....74 Research Design……………………………………………………………….77 ii Data Analysis and Statistics…………………………………………………...78 IV. Results………………………………………………………………………….79 Characterization of Spinal Cord, Cortical and Deep Gray Matter Lesions in the Absence of White Matter Lesions……………………………………………..79 Characterization of Spinal Cord Demyelination of Classical and Myelocortical MS Patients…………………………………………………………………….81 Characterization of Cortical Demyelination of Classical and Myelocortical MS Patients………………………………………………..……………………….84 Characterization of Demyelination and association with meningeal inflammation on Hemispheric Sections………………………………………………………88 Characterization of Hippocampal Lesions in Classical and Myelocortical MS Patients………………………………………………..……………………….89 Characterization of Thalamic Lesions of Classical and Myelocortical MS Patients………………………………………………..……………………….91 Identification of Lesions in the Brainstem of Classical and Myelocortical MS Patients………………………………………………..……………………….92 Summary of Histological examination of CNS of Classical and Myelocortical MS Patients………………………………………………..……………………….93 Pathology Underlying Magnetic Resonance Imaging Abnormal Signals in Myelocortical MS Patients…………………………………………………….94 MRI-Defined Normal Appearing White Matter in Myelocortical MS………..95 MRI-Defined T2-Only Regions in Myelocortical MS………………………...96 MRI-Defined T2T1MTR Regions in Myelocortical MS………………….…..97 Atrophy and White Matter Lesion Volumes by MRI………………………..104 Comparing Whole Brain Atrophy Between Controls, Classical and Myelocortical MS…………………………………………………………………………….106 V. Conclusions and Discussion………………………………………………......110 Summary of Major Findings………………………………………………….110 Conclusions…………………………………………………………………...112 Importance of the Studies in Management of MS……....…………………….120 Impact Statement…………………………………………………………...…128 Limitations of the Thesis…………………………………………….………..129 Recommendations for Future Research………………………………………131 Removal of Inhibitors of Remyelination…………………………………..…131 Mechanism of Cortical Demyelination…………………………………..…..145 Closing Remarks……………………………………………………………..151 List of References…………………………………………………………………………….153 iii List of Figures Figure 1: Schematic of Multiple Sclerosis Progression Figure 2: Methods of MRI White Matter Region Selection Figure 3: Methods of Lesion Load Measurements Figure 4: Cerebral White Matter Lesion Loads Figure 5: Spinal Cord Lesion Loads Figure 6: Cortical Gray Matter Lesion Loads Figure 7: Coronal Images of Classical and Myelocortical MS Figure 8: Peripheral Inflammatory Cell Counts Figure 9: Hippocampal Demyelination Figure 10: Histology of MRI Defined White Matter Regions Figure 11: Myelin and Axonal Densities in MRI Regions Figure 12: MRI Scans from Classical and Myelocortical MS Patients Figure 13: Disease Mechanisms of the Multiple Sclerosis Spectrum Figure 14: Sox9 Staining in MS and Control Tissue Figure 15: Sox9 Staining in Cuprizone Mouse Model Figure 16: Sox9 Expression Pattern in MS White and Gray Matter Lesions Figure 17: Elimination of Cell Types Not Expressing Sox9 Figure 18: Astrocyte Labeling of Sox9 Figure 19: Cortical Myelin Density for MS and Control Patients Figure 20: Oligodendrocyte Morphometry and Internodal Length Figure 21: Myelin Protein Degeneration iv List of Tables Table 1: Patient Demographics Table 2: Disease Modifying Therapies Table 3: Magnetic Resonance Imaging Guided Histopathological Analysis of Myelocortical Multiple Sclerosis White Matter Table 4: Magnetic Resonance Imaging Characteristics of Myelocortical Multiple Sclerosis and Classical Multiple Sclerosis Patients v Special Recognitions I must extend my overwhelming gratitude to those that have been on this journey with me. I first wish to thank my mother and father for instilling in me a work ethic and a thirst for knowledge that have suited me well in this expedition for my doctorate. Next, I need to thank my husband for the love, support and encouragement he has given me over these years and never doubted that I could and would complete this work. I want to thank my friends that have been beside me through the highs and the lows of a science career. Lastly, I want to thank my two nieces for reminding me to laugh, smile and just enjoy life. vi Further Acknowledgements With regards to the work in the following thesis, I want to thank: Dr. Bruce Trapp: For supervising the entirety of this work and advising all aspects of my doctoral thesis. Dr. Ansi Chang: For providing training of immunohistochemical staining, coordinating the Rapid MS Autopsy Program, advice and other technical support. Dr. Zhihong Chen: For providing several analysis techniques, constant feedback and meaningful advice and discussions over the years. Dr. Elizabeth Fisher: For her extensive contributions to my thesis work, her insightful discussions and mentorship. Drs. Jennifer McDonough, Robert Dorman, MaryAnn Raghanti, and Marilyn Norconk: For serving on my PhD guidance committee, teaching me numerous lessons, and for giving countless pieces of advice on my thesis work. Drs. Susan Staugaitis and Robert Fox: For their involvement in the Rapid MS Autopsy Program and for providing helpful suggestions on the direction of my thesis work and manuscript. Dr. Sverre Mork: For teaching me the techniques for hemispheric sectioning, and for his stimulating discussions. Dr. Jacqueline Chen: For teaching me repeatedly about the inner workings of MRI, fascinating discussions, singing 80’s songs with me in the lab, and for much needed support and encouragement. vii Dr. Chris Nelson: For editing manuscripts, my prospectus and my thesis as well as providing advice and support. Drs. Ranjan Dutta and Grahame Kidd: For their discussions on presentations, image processing, data analysis, and advice on manuscripts. Trapp Lab members, of which there have been many over the years: For their support, monkey business, camaraderie, and hard work in the autopsy program. Lastly, I would like to thank the MS patient donors and their families, for without their generous and significant contributions this work would never have come to fruition. viii Chapter 1 Section 1: Introduction Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease with underlying neurodegeneration of the human central nervous system, which affects over 2.3 million individuals worldwide and currently has no cure. This disease affects 2 times more females than males and is the major cause of non-traumatic neurological disability in young adults, with onset occurring often in the third decade of life (average age 25-33, (1), although pediatric MS also occurs in those 18 years old and younger). The etiology of MS involves a complex relationship between environment and genetic susceptibility. The environmental factors that have been proposed to play a role in MS etiology and risk range from (A) sunlight exposure which is also highly connected to vitamin D status, with an increased prevalence of MS for individuals residing further from the equator; (B) smoking; and (C) infections from viruses like Epstein - Barr virus and human endogenous retrovirus-W. Although these factors seem to play a role in the risk for developing MS, how they actually affect different aspects of the disease, including the onset or course of the disease, is largely unknown. Genetics also play a role in susceptibility to this disease, as demonstrated by the fact that the risk of developing MS increases in those individuals with a family history of the disease, particularly in immediate family members (2). Twin studies have demonstrated an increased concordance rate of 31% in monozygotic twins, compared to 5% for dizygotic twins (3). A specific allele has been identified 1 as carrying a risk of 16-60% chance of developing MS (4). The gene is for the Human Leucocyte Antigen (HLA) Class II locus, which is part of the major histocompatibility complex located on chromosome 6p21 and has been shown to have a dose effect of
Load more

Recommended publications
  • Ilya Mark Scheinker: Controversial Neuroscientist and Refugee from National Socialist Europe
    HISTORICAL ARTICLE COPYRIGHT © 2016 THE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES INC. Ilya Mark Scheinker: Controversial Neuroscientist and Refugee From National Socialist Europe Lawrence A. Zeidman, Matthias Georg Ziller, Michael Shevell ABSTRACT: Russian-born, Vienna-trained neurologist and neuropathologist Ilya Mark Scheinker collaborated with Josef Gerstmann and Ernst Sträussler in 1936 to describe the familial prion disorder now known as Gerstmann-Sträussler-Scheinker disease. Because of Nazi persecution following the annexation of Austria by Nazi Germany, Scheinker fled from Vienna to Paris, then after the German invasion of France, to New York. With the help of neurologist Tracy Putnam, Scheinker ended up at the University of Cincinnati, although his position was never guaranteed. He more than doubled his prior publications in America, and authored three landmark neuropathology textbooks. Despite his publications, he was denied tenure and had difficulty professionally in the Midwest because of prejudice against his European mannerisms. He moved back to New York for personal reasons in 1952, dying prematurely just 2 years later. Scheinker was twice uprooted, but persevered and eventually found some success as a refugee. RÉSUMÉ: Ilya Mark Scheinker, un spécialiste des neurosciences et un réfugié de l’Europe nationale-socialiste controversé. Ilya Mark Scheinker était né en Russie et il avait fait ses études de neurologie et de neuropathologie à Vienne. Il a collaboré avec Josef Gerstmann et Ernst Sträussler en 1936 pour décrire la maladie familiale à prions connue maintenant sous le nom de maladie de Gerstmann-Sträussler. En raison de la persécution Nazi qui a suivi l’annexion de l’Autriche par l’Allemagne nazie, Scheinker a fui Vienne pour s’établir à Paris puis à New-York après l’invasion de la France par l’Allemagne.
    [Show full text]
  • Positron Emission Tomography in Aging and Dementia: Effect of Cerebral Atrophy
    CLINICAL SCIENCES Positron Emission Tomography in Aging and Dementia: Effect of Cerebral Atrophy John B. Chawluk, Abass Alavi, Robert Dann, Howard I. Hurtig, Sanjiv Bais, Michael J. Kushner, Robert A. Zimmerman, and Martin Reivich Department of Neurology, Cerebrovascular Research Center, and Department of Radiology. Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania The spatial resolution of current positron emission tomography (PET) scanners does not allow a distinction between cerebrospinal fluid (CSF) containing spaces and contiguous brain tissue. Data analysis strategies which therefore purport to quantify cerebral metabolism per unit mass brain tissue are in fact measuring a value which may be artifactually reduced due to contamination by CSF. We studied cerebral glucose metabolism (CMRglc) in 17 healthy elderly individuals and 24 patients with Alzheimer's dementia using [18F]fluorodeoxyglucose and PET. All subjects underwent x-ray computed tomography (XCT) scanning at the time of their PET study. The XCT scans were analyzed volumetrically, in order to determine relative areas for ventricles, sulci, and brain tissue. Global CMRglc was calculated before and after correction for contamination by CSF (cerebral atrophy). A greater increase in global CMRglc after atrophy correction was seen in demented individuals compared with elderly controls (16.9% versus 9.0%, p < 0.0005). Additional preliminary data suggest that volumetric analysis of proton-NMR images may prove superior to analysis of XCT data in quantifying the degree of atrophy. Appropriate corrections for atrophy should be employed if current PET scanners are to accurately measure actual brain tissue metabolism in various pathologic states. J NucíMed 28:431-^137,1987 he pioneering nitrous oxide technique of Kety and inability to measure glucose or oxygen metabolism Schmidt first enabled investigators to measure global directly.
    [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]
  • Trh15. Subdural Hygroma.Pdf
    SUBDURAL HYGROMA TrH15 (1) Subdural Hygroma (s. Subdural Effusion) Last updated: April 20, 2019 ETIOLOGY, PATHOPHYSIOLOGY ............................................................................................................. 1 Further course ................................................................................................................................... 1 CLINICAL FEATURES ............................................................................................................................... 1 Complications ................................................................................................................................... 1 DIAGNOSIS................................................................................................................................................ 1 TREATMENT ............................................................................................................................................. 3 SUBDURAL HYGROMA - excessive CSF collection in subdural space. [Greek hygros – wet] ETIOLOGY, PATHOPHYSIOLOGY 1. MOST COMMON CAUSE - cranial trauma with arachnoid tearing and arachnoid-dura separation (→ CSF escape into subdural space) - TRAUMATIC SUBDURAL HYGROMA. – develops in ≈ 10% severe head injuries. – skull fractures are found in 39% cases. – predisposing factors: cerebral atrophy (present in 19% hygromas), vigorous therapeutic dehydration (iatrogenic brain collapse), intracranial hypotension (e.g. in prolonged lumbar drainage), pulmonary hypertension (e.g.
    [Show full text]
  • Inflammation, Demyelination, and Degeneration
    Biochimica et Biophysica Acta 1812 (2011) 275–282 Contents lists available at ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbadis Review Inflammation, demyelination, and degeneration — Recent insights from MS pathology Christine Stadelmann ⁎, Christiane Wegner, Wolfgang Brück Institute of Neuropathology, University Medical Centre, Göttingen, Germany article info abstract Article history: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system which responds to Received 15 March 2010 anti-inflammatory treatments in the early disease phase. However, the pathogenesis of the progressive Received in revised form 30 June 2010 disease phase is less well understood, and inflammatory as well as neurodegenerative mechanisms of tissue Accepted 6 July 2010 damage are currently being discussed. This review summarizes current knowledge on the interrelation Available online 15 July 2010 between inflammation, demyelination, and neurodegeneration derived from the study of human autopsy and biopsy brain tissue and experimental models of MS. Keywords: Multiple sclerosis © 2010 Elsevier B.V. All rights reserved. Pathogenesis Pathology Neuroaxonal damage Autoimmunity Progressive disease 1. Introduction in MS is necessarily the myelin sheath or oligodendrocyte [4].This review summarizes current knowledge and recent advances in MS Multiple sclerosis (MS) is an inflammatory demyelinating CNS immunopathology. disease frequently starting in young adulthood. Supported by experimental evidence mainly derived from its principal model, 2. Inflammation and demyelination experimental allergic encephalomyelitis (EAE), MS is generally considered a predominantly T cell-mediated autoimmune disease MS lesions can arise anywhere in the CNS. However, they show a [1]. In line with this notion, immunomodulatory and anti-inflamma- predilection for the optic nerve, spinal cord, brain stem, and tory therapies prove to be effective, especially early in the disease periventricular areas.
    [Show full text]
  • Stepping out to Support People with MS
    The Official Magazine of MS Australia – ACT/NSW/VIC www.msaustralia.org.au/actnswvic ISSN 1833-8941 Print Post Approved: Spring 2012 PP 255003/08108 Sandra The types of MS explained The benefits of Sully aquatic exercise Stepping out to support Spotlight on: people with MS Respite services New series: MS Awareness Emerging MS Month: treatments Highlights! www.facebook.com/MSAustralia http://twitter.com/MS_Australia www.youtube.com/MSSocietyAustralia Co-editors: Rebecca Kenyon & Sandra Helou Publisher: Multiple Sclerosis Limited ABN: 66 004 942 287 Website: www.msaustralia.org.au/actnswvic Frequency: Published quarterly in March, June, September, December Advertising enquiries: Tel: (02) 9646 0725, Fax: (02) 9643 1486, Email: [email protected] Design: Byssus, (02) 9482 5116, www.byssus.com.au Photographs: The stock images appearing in Intouch are sourced from Thinkstock.com Cover photography: Dan Freede Photography Printing: Webstar Print MS Australia – ACT/NSW/VIC ACT Gloria McKerrow House 117 Denison Street Deakin ACT 2600 Tel: (02) 6234 7000 Fax: (02) 6234 7099 12 NSW Studdy MS Centre 80 Betty Cuthbert Dr Lidcombe NSW 2141 Tel: (02) 9646 0600 Fax: (02) 9643 1486 Victoria The Nerve Centre 16 54 Railway Road Blackburn VIC 3130 Tel: (03) 9845 2700 Fax: (03) 9845 2777 11 MS ConnectTM (information and services): 1800 042 138 (free call) Regional offices: Visit www.msaustralia.org.au/actnswvic and click on ‘Contact Us’ Privacy Policy: Visit www.msaustralia.org.au/ actnswvic for our full policy document ISSN: 1833-8941 Disclaimer: Information and articles contained in Intouch are intended to provide useful and accurate information of a general nature for the reader but are not intended to be a substitute Take our Client Satisfaction Survey for legal or medical advice.
    [Show full text]
  • And Cerebral Atrophy in Senile Dementia
    J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.39.8.751 on 1 August 1976. Downloaded from Journal ofNeurology, Neurosurgery, and Psychiatry, 1976, 39, 751-755 Correlation between diffuse EEG abnormalities and cerebral atrophy in senile dementia DUSAN STEFOSKI, DONNA BERGEN, JACOB FOX, FRANK MORRELL, MICHAEL HUCKMAN, AND RUTH RAMSEY From the Department ofNeurological Sciences and Department ofDiagnostic Radiology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois, USA SYNOPSIS Thirty-five elderly patients were investigated because of clinical signs of dementia. The presence of diffuse cerebral atrophy, and its severity, were determined by the use of computed tomog- raphy (CT scan). All of the patients were also examined by electroencephalography (EEG), and the presence of diffuse abnormalities, especially diffuse slowing, was noted. Specifically, patients with normal or near-normal EEGs were compared with those with severe diffuse slowing. No correlation guest. Protected by copyright. between the presence or severity of diffuse EEG abnormalities and the degree of cerebral atrophy as measured by CT scan was found. Though the EEG is clearly identifying physiological dysfunction of nerve cells in demented patients it does not appear to be a reliable tool for the prediction of diffuse cerebral atrophy in this population. Senile dementia in association with diffuse defined as the gradual onset of intellectual deteriora- cerebral atrophy is one of the problems com- tion after the age of 59 years. Those patients with a monly encountered by the clinical neurologist. In past history of strokes or major focal findings on the numerous studies the EEG of demented indi- neurological examination were excluded.
    [Show full text]
  • WASTE PAPER Colleaion a NEW HOME?
    . t v C » A s ^ c m n cr. xuHB 11. i n t t!40B TWELVE jKanrh^etrr Etintitts if^roUi D ll^ !l*l Pl6m 1 " i- there Is some danger thet flee, ■us to the stoeu auaagers. We w cosm ■ '" thrown helter-okelter e t nupOels, know they will M eay ooo- Green School 5509 About Town sMgkt egrout eU over churob Btruetlva ertUelem oCfered. Heard Along Main Street Uwan. Wild rise being eown In ARMY AND NAVY CLUB MMlt pleeoo n d i^ t net bo mgerdod “Besrfi AMag” really did hear t k i n a <Man «m koU thatr Gives Program C ky o f V V o f Chmrm And on Soma of Manehe$Ut^» Stdo SfrM fg, Too an the best thing. They b m tried the other day thet the new bus c a m «a H a f Uila afUmeoB Bt R with oets bofore, end It has not loop scbedulea from Hartford to tbt OBiiiiinrtrT- A buffet lunch Manchester Green vie Mein and proven popular. i i t e * ru g s m MANCHESTER, CONN., MONDAY, JI7NE 14, 1948 fFOURTBEN PAGES) P R IC tfO U ti trtn be eerred et three o’clock end A mother of two children celled » stope, were pussled by the deerth This buslneas o f adapting e crop Woodbridge etreeta. namely bueee Kindergarten and See> NEW SUPER VOL. Lxvn ., NO; u end epeghetti eupper et heeding out to the Green end re­ in to regloUr her obJecUon to of custonsere to n ktonUty has us pretty well ond Grade Pkeaent Children’s Dey progrems in the Let us look beck.
    [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]
  • 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]
  • Stroke Subtype, Vascular Risk Factors, and Total MRI Brain Small-Vessel Disease Burden
    ARTICLES Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden Julie Staals, MD, PhD ABSTRACT Stephen D.J. Makin, Objectives: In this cross-sectional study, we tested the construct validity of a “total SVD score,” MBChB which combines individual MRI features of small-vessel disease (SVD) in one measure, by testing Fergus N. Doubal, associations with vascular risk factors and stroke subtype. MBChB, PhD Methods: We analyzed data from patients with lacunar or nondisabling cortical stroke from 2 pro- Martin S. Dennis, spective stroke studies. Brain MRI was rated for the presence of lacunes, white matter hyperin- MBChB, MD, FRCP tensities, cerebral microbleeds, and perivascular spaces independently. The presence of each Joanna M. Wardlaw, SVD feature was summed in an ordinal “SVD score” (range 0–4). We tested associations with MBChB, MD, FRCR vascular risk factors, stroke subtype, and cerebral atrophy using ordinal regression analysis. Results: In 461 patients, multivariable analysis found that age (odds ratio [OR] 1.10, 95% confi- Correspondence to dence interval [CI] 1.08–1.12), male sex (OR 1.58, 95% CI 1.10–2.29), hypertension (OR 1.50, Dr. Wardlaw: 95% CI 1.02–2.20), smoking (OR 2.81, 95% CI 1.59–3.63), and lacunar stroke subtype (OR [email protected] 2.45, 95% CI 1.70–3.54) were significantly and independently associated with the total SVD score. The score was not associated with cerebral atrophy. Conclusions: The total SVD score may provide a more complete estimate of the full impact of SVD on the brain, in a simple and pragmatic way.
    [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]