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Journal Article•DOI•

Diagnosis of multiple sclerosis: progress and challenges

Wallace J Brownlee1, Todd A. Hardy2, Franz Fazekas3, David Miller4, David Miller1 •
University College London1, University of Sydney2, Medical University of Graz3, National Institute for Health Research4
01 Apr 2017-The Lancet (Elsevier)-Vol. 389, Iss: 10076, pp 1336-1346
TL;DR: The progress and challenges in the diagnosis of multiple sclerosis with reference to diagnostic criteria, important differential diagnoses, controversies and uncertainties, and future prospects are explored.
About: This article is published in The Lancet.The article was published on 2017-04-01 and is currently open access. It has received 404 citations till now. The article focuses on the topics: Multiple sclerosis & Acute disseminated encephalomyelitis.

Summary (3 min read)

Jump to: [Introduction] – [Presenting symptoms of MS] – [The radiologically isolated syndrome] – [MS in children] – [MS in older adults] – [Atypical demyelinating lesions] – [Differential diagnosis of MS] – [Acute disseminated encephalomyelitis (ADEM)] – [Misdiagnosis of multiple sclerosis] – [Controversies and areas of uncertainty] and [Conclusions and future perspectives]

Introduction

  • Multiple sclerosis (MS) is a chronic, immune-mediated demyelinating disorder of the central nervous system (CNS).
  • Recovery from relapses is variable and may be incomplete.
  • There is evidence that the incidence of RRMS may be increasing, particularly in women.3 PPMS (10-15% of patients) is characterised by an insidious, slowly progressive increase in neurological disability over time, usually without relapses.
  • Currently, the diagnosis is based on clinical symptoms and signs and magnetic resonance imaging (MRI), which is highly sensitive to the detection of characteristic CNS lesions.
  • Advances in MRI, immunological and genetic tests have improved the diagnosis of other conditions that can be mistaken for MS.

Presenting symptoms of MS

  • The initial presentation of MS is varied and depends both on the location of lesions within the CNS and their onset (relapsing or progressive).
  • Clinical features that suggest demyelination as the cause of such an episode include age <40 years, an acute/subacute onset over hours to days, maximal deficit within 4 weeks of onset and spontaneous remission.
  • 14 Qualitative assessment of IgG using isoelectric focusing and immunofixation is the optimal method for detection of OCBs.
  • Using the McDonald 2010 criteria a diagnosis of MS can still be made on clinical grounds alone; however, MRI is used to provide evidence for dissemination in time and space, including in patients with CIS.1.
  • Dissemination in time requires either asymptomatic gadolinium-enhancing and non-enhancing lesions on the same MRI scan or a new lesion on a follow up scan.

The radiologically isolated syndrome

  • The widespread use of MRI means incidental findings suggestive of MS are sometimes identified in some people who have no clinical symptoms.
  • The typical demyelinating lesions that characterise RIS need to be carefully differentiated from small-vessel cerebrovascular disease and nonspecific white matter lesions (the latter being common in people with migraine21,24).
  • 29 Younger age, male gender and gadolinium-enhancing, cortical or spinal cord lesions may be associated with an increased risk of developing MS.2931.
  • There are no accepted diagnostic criteria for RIS, but the Okuda 2009 criteria28 have been used in research studies and can also be applied in a clinical setting.
  • These criteria consider only dissemination in space and are more stringent than the McDonald criteria, taking into account lesion size and morphology as well as location to help differentiate asymptomatic demyelinating lesions from other white matter lesions.

MS in children

  • In younger children (<12 years) MS may present differently from adolescents and adults; encephalopathy, multifocal neurological deficits (often with prominent brainstem/cerebellar involvement) and seizures are more common.
  • 32 MRI findings may include large, confluent T2-hyperintense lesions that show remarkable resolution on followup scans.33.
  • The clinical features and MRI findings may be suggestive of ADEM (see below).
  • Older children (≥12 years) usually present with clinical features and MRI findings similar to adults with CIS.32,34.
  • The performance of the McDonald 2010 criteria has been tested in children with CIS and the criteria have a similar sensitivity/specificity for the development of MS as in adult populations35 but should not be applied in the setting of encephalopathy (i.e. ADEM).32.

MS in older adults

  • People presenting with MS after the age of 50 years have typically been classified as having late-onset multiple sclerosis.36.
  • In this age group males are over-represented and a progressive onset is more common.
  • Establishing a diagnosis of MS can be more difficult in older adults because white matter lesions due to small-vessel cerebrovascular disease are frequently found on brain MRI.
  • Studies investigating MRI criteria for a diagnosis of MS have typically excluded patients older than 50 years and the McDonald criteria have not been investigated in this group.

Atypical demyelinating lesions

  • Brain lesions in MS are typically small (<1cm diameter) and ovoid with a homogenous signal on T2-weighted sequences.9.
  • Occasionally, MS presents with an atypical demyelinating lesion characterised by their large size (>2cm diameter, sometimes with peri-lesional oedema and mass effect), enhancement pattern (open or closed-ring enhancement) or morphology (infiltrative or heterogeneous appearance including concentric rings).
  • 38-40 These lesions may have the appearance of a neoplasm (glioma, primary CNS lymphoma) or infection (brain abscess, progressive multifocal leukoencephalopathy), sometimes necessitating brain biopsy.
  • While some patients presenting with atypical demyelinating lesions have a monophasic course, 30-60% develop MS.38,40 MRI might help predict outcome; the presence of typical MS lesions and a closed-ring enhancement pattern have been associated with a higher risk of MS.38 Atypical demyelinating lesions are also seen in NMOSD and ADEM.

Differential diagnosis of MS

  • The differential diagnosis of MS is broad and many neurologists use the approach of identifying “red flag” clinical, imaging or other laboratory features that suggest an alternative diagnosis.
  • The differential diagnosis depends on the clinical presentation with different considerations in patients with relapsing or progressive courses.
  • These disorders include several closely related idiopathic inflammatory CNS diseases, along with a range of other disorders that may involve white matter including inherited leukodystrophies, vasculopathies, metabolic disorders and other neuroinflammatory diseases (e.g. sarcoidosis, vasculitis, Behcet’s disease).
  • Tables 2 and 3 provide further information on a limited number of disorders that, in their experience, can be confused with MS.
  • Selected idiopathic inflammatory disorders in which demyelination is a feature are discussed in more detail below.

Acute disseminated encephalomyelitis (ADEM)

  • Patients present with multifocal neurological deficits and encephalopathy sometimes with a history of antecedent infection or vaccination.
  • 42 CSF findings include a lymphocytic pleocytosis and raised protein.
  • 45,47 An accurate diagnosis of NMOSD is essential since prompt treatment of acute attacks and long-term immunosuppression appear to reduce disability, while conventional MS treatments may aggravate NMOSD.44,48.
  • The core clinical features of NMOSD are optic neuritis and transverse myelitis.
  • Routine testing for AQP4-IgG in CIS populations with a high incidence of MS and low incidence of NMOSD has a very low yield and is not recommended.

Misdiagnosis of multiple sclerosis

  • In a survey of MS specialist neurologists in the United States, 95% of respondents had seen one or more patients in the previous year who had been misdiagnosed with MS, many of whom were being treated inappropriately with disease-modifying therapies.
  • The major disorders identified that were misdiagnosed as MS were small-vessel cerebrovascular disease, migraine, fibromyalgia and functional neurological disorders.
  • These disorders usually present quite differently to MS and reasons for misdiagnosis included misinterpretation of clinical findings (symptoms not typical of demyelination, absence of objective neurological signs) and inappropriate application of MRI criteria.
  • The application of McDonald criteria and the diagnosis of MS should be undertaken by neurologists who are familiar with MS with additional expert advice when needed (e.g. MRI review by a neuroradiologist).

Controversies and areas of uncertainty

  • The role of spinal cord imaging65 and CSF examination66 in MS diagnosis is particularly controversial.
  • 12 The United States Food and Drug Administration and the European Medicines Agency are investigating the clinical significance of gadolinium deposits in the brain reported in some patients after the repeated use of gadolinium-based contrast agents.
  • 19 However, the criteria are intended to provide diagnostic rather than prognostic information.
  • Conventional brain MRI findings around the time of diagnosis are only modestly predictive of long-term disability8 and there is uncertainty as to the extent to which criteria for diagnosis and treatment should be linked.

Conclusions and future perspectives

  • Current diagnostic criteria for MS integrate clinical and MRI findings and enable an earlier and more reliable diagnosis of MS than with clinical findings alone, potentially facilitating earlier treatment.
  • Brain MRI is abnormal during the acute (three-month) phase.
  • Exclusion of alternative diagnoses Supplementary Figure 1. T2-weighted MRI scans in AQP4-IgG positive neuromyelitis optica spectrum disorder .
  • Where appropriate review articles have been referenced to provide more detailed information on individual topics.

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Citations
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Journal Article•DOI•
Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

[...]

Alan J. Thompson1, Brenda Banwell2, Frederik Barkhof3, Frederik Barkhof1, William M. Carroll4, Timothy Coetzee5, Giancarlo Comi6, Jorge Correale, Franz Fazekas7, Massimo Filippi6, Mark S. Freedman8, Kazuo Fujihara9, Steven L. Galetta10, Hans-Peter Hartung11, Ludwig Kappos12, Fred D. Lublin13, Ruth Ann Marrie14, Aaron E. Miller13, David Miller1, Xavier Montalban15, Xavier Montalban16, Ellen M. Mowry17, Per Soelberg Sørensen18, Mar Tintoré15, Anthony Traboulsee19, Maria Trojano20, Bernard M. J. Uitdehaag3, Sandra Vukusic21, Sandra Vukusic22, Emmanuelle Waubant23, Brian G. Weinshenker24, Stephen C. Reingold25, Jeffrey A. Cohen26 •
University College London1, Children's Hospital of Philadelphia2, VU University Medical Center3, Sir Charles Gairdner Hospital4, National Multiple Sclerosis Society5, Vita-Salute San Raffaele University6, Medical University of Graz7, Ottawa Hospital Research Institute8, Fukushima Medical University9, New York University10, University of Düsseldorf11, University of Basel12, Corinne Goldsmith Dickinson Center for Multiple Sclerosis13, University of Manitoba14, Hebron University15, St. Michael's Hospital16, Johns Hopkins University17, University of Copenhagen18, University of British Columbia19, University of Bari20, French Institute of Health and Medical Research21, Claude Bernard University Lyon 122, University of California, San Francisco23, Mayo Clinic24, Salisbury University25, Cleveland Clinic26
21 Dec 2017-Lancet Neurology
TL;DR: The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation.
Abstract: The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.

3,945 citations

Journal Article•DOI•
Neurofilaments as biomarkers in neurological disorders

[...]

Michael Khalil1, Charlotte E. Teunissen2, Markus Otto3, Fredrik Piehl4, Maria Pia Sormani5, Thomas Gattringer1, Christian Barro6, Ludwig Kappos6, Manuel Comabella7, Franz Fazekas1, Axel Petzold8, Kaj Blennow9, Kaj Blennow10, Henrik Zetterberg, Jens Kuhle6 •
Medical University of Graz1, University of Amsterdam2, University of Ulm3, Karolinska Institutet4, University of Genoa5, University Hospital of Basel6, Autonomous University of Barcelona7, UCL Institute of Neurology8, University of Gothenburg9, Sahlgrenska University Hospital10
31 Aug 2018-Nature Reviews Neurology
TL;DR: How technological advances have enabled the detection of neurofilament proteins in the blood is considered, and how these proteins consequently have the potential to be easily measured biomarkers of neuroaxonal injury in various neurological conditions are discussed.
Abstract: Neuroaxonal damage is the pathological substrate of permanent disability in various neurological disorders. Reliable quantification and longitudinal follow-up of such damage are important for assessing disease activity, monitoring treatment responses, facilitating treatment development and determining prognosis. The neurofilament proteins have promise in this context because their levels rise upon neuroaxonal damage not only in the cerebrospinal fluid (CSF) but also in blood, and they indicate neuroaxonal injury independent of causal pathways. First-generation (immunoblot) and second-generation (enzyme-linked immunosorbent assay) neurofilament assays had limited sensitivity. Third-generation (electrochemiluminescence) and particularly fourth-generation (single-molecule array) assays enable the reliable measurement of neurofilaments throughout the range of concentrations found in blood samples. This technological advancement has paved the way to investigate neurofilaments in a range of neurological disorders. Here, we review what is known about the structure and function of neurofilaments, discuss analytical aspects and knowledge of age-dependent normal ranges of neurofilaments and provide a comprehensive overview of studies on neurofilament light chain as a marker of axonal injury in different neurological disorders, including multiple sclerosis, neurodegenerative dementia, stroke, traumatic brain injury, amyotrophic lateral sclerosis and Parkinson disease. We also consider work needed to explore the value of this axonal damage marker in managing neurological diseases in daily practice.

1,038 citations

Journal Article•DOI•
The role of the gut microbiome in systemic inflammatory disease

[...]

Jose C. Clemente1, Julia Manasson2, Jose U. Scher2•
Icahn School of Medicine at Mount Sinai1, New York University2
08 Jan 2018-BMJ
TL;DR: This review summarizes the preclinical and clinical evidence on how dietary, probiotic, prebiotic, and microbiome based therapeutics affect the understanding of wellness and disease, particularly in autoimmunity.
Abstract: The role of the gut microbiome in models of inflammatory and autoimmune disease is now well characterized. Renewed interest in the human microbiome and its metabolites, as well as notable advances in host mucosal immunology, has opened multiple avenues of research to potentially modulate inflammatory responses. The complexity and interdependence of these diet-microbe-metabolite-host interactions are rapidly being unraveled. Importantly, most of the progress in the field comes from new knowledge about the functional properties of these microorganisms in physiology and their effect in mucosal immunity and distal inflammation. This review summarizes the preclinical and clinical evidence on how dietary, probiotic, prebiotic, and microbiome based therapeutics affect our understanding of wellness and disease, particularly in autoimmunity.

336 citations

Journal Article•DOI•
Multiple sclerosis: clinical aspects.

[...]

Jiwon Oh1, Angela Vidal-Jordana2, Xavier Montalban1, Xavier Montalban2•
University of Toronto1, Autonomous University of Barcelona2
01 Dec 2018-Current Opinion in Neurology
TL;DR: The epidemiology, diagnosis, disease course, and prognosis of multiple sclerosis is discussed and a combination of clinical, imaging, and laboratory markers can be useful in predicting clinical course and optimizing treatment in individual patients.
Abstract: Purpose of review Multiple sclerosis is a chronic, predominantly immune-mediated disease of the central nervous system, and one of the most common causes of neurological disability in young adults globally. This review will discuss the epidemiology, diagnosis, disease course, and prognosis of multiple sclerosis and will focus on recent evidence and advances in these aspects of the disease. Recent findings Multiple sclerosis is increasing in incidence and prevalence globally, even in traditionally low-prevalence regions of the world. Recent revisions have been proposed to the existing multiple sclerosis diagnostic criteria, which will facilitate earlier diagnosis and treatment in appropriate patients. Classifying multiple sclerosis into distinct disease phenotypes can be challenging, and recent refinements have been proposed to clarify existing definitions. The prognosis of multiple sclerosis varies substantially across individual patients, and a combination of clinical, imaging, and laboratory markers can be useful in predicting clinical course and optimizing treatment in individual patients. Summary A number of recent advances have been made in the clinical diagnosis and prognostication of multiple sclerosis patients. Future research will enable the development of more accurate biomarkers of disease categorization and prognosis, which will enable timely personalized treatment in individual multiple sclerosis patients.

243 citations

Journal Article•DOI•
The burden of neurological diseases in Europe: an analysis for the Global Burden of Disease Study 2017.

[...]

Günther Deuschl1, Günther Deuschl2, Ettore Beghi1, Ettore Beghi3, Franz Fazekas1, Franz Fazekas4, Timea Varga1, Kalliopi A Christoforidi1, Eveline Sipido1, Claudio L. Bassetti1, Claudio L. Bassetti5, Theo Vos6, Theo Vos7, Valery L. Feigin6, Valery L. Feigin8 •
European Academy of Neurology1, University of Kiel2, Mario Negri Institute for Pharmacological Research3, University of Graz4, University of Bern5, Institute for Health Metrics and Evaluation6, University of Washington7, Auckland University of Technology8
01 Oct 2020-The Lancet. Public health
TL;DR: The burden of neurological disorders in Europe was higher in men than in women, peaked in individuals aged 80-84 years, and varied substantially with WHO European region and country.
Abstract: Summary Background Neurological disorders account for a large and increasing health burden worldwide, as shown in the Global Burden of Diseases (GBD) Study 2016. Unpacking how this burden varies regionally and nationally is important to inform public health policy and prevention strategies. The population in the EU is older than that of the WHO European region (western, central, and eastern Europe) and even older than the global population, suggesting that it might be particularly vulnerable to an increasing burden of age-related neurological disorders. We aimed to compare the burden of neurological disorders in the EU between 1990 and 2017 with those of the WHO European region and worldwide. Methods The burden of neurological disorders was calculated for the year 2017 as incidence, prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost, and years lived with disability for the countries in the EU and the WHO European region, totally and, separately. Diseases analysed were Alzheimer's disease and other dementias, epilepsy, headache (migraine and tension-type headache), multiple sclerosis, Parkinson's disease, brain cancer, motor neuron diseases, neuroinfectious diseases, and stroke. Data are presented as totals and by sex, age, year, location and socio-demographic context, and shown as counts and rates. Findings In 2017, the total number of DALYs attributable to neurological disorders was 21·0 million (95% uncertainty interval 18·5–23·9) in the EU and 41·1 million (36·7–45·9) in the WHO European region, and the total number of deaths was 1·1 million (1·09–1·14) in the EU and 1·97 million (1·95–2·01) in the WHO European region. In the EU, neurological disorders ranked third after cardiovascular diseases and cancers representing 13·3% (10·3–17·1) of total DALYs and 19·5% (18·0–21·3) of total deaths. Stroke, dementias, and headache were the three commonest causes of DALYs in the EU. Stroke was also the leading cause of DALYs in the WHO European region. During the study period we found a substantial increase in the all-age burden of neurodegenerative diseases, despite a substantial decrease in the rates of stroke and infections. The burden of neurological disorders in Europe was higher in men than in women, peaked in individuals aged 80–84 years, and varied substantially with WHO European region and country. All-age DALYs, deaths, and prevalence of neurological disorders increased in all-age measures, but decreased when using age-standardised measures in all but three countries (Azerbaijan, Turkmenistan, and Uzbekistan). The decrease was mostly attributed to the reduction of premature mortality despite an overall increase in the number of DALYs. Interpretation Neurological disorders are the third most common cause of disability and premature death in the EU and their prevalence and burden will likely increase with the progressive ageing of the European population. Greater attention to neurological diseases must be paid by health authorities for prevention and care. The data presented here suggest different priorities for health service development and resource allocation in different countries. Funding European Academy of Neurology.

218 citations

References
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Journal Article•DOI•
Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria

[...]

Chris H. Polman1, Stephen C. Reingold, Brenda Banwell2, Michel Clanet3, Jeffrey A. Cohen4, Massimo Filippi, Kazuo Fujihara5, Eva Havrdova6, Michael Hutchinson7, Ludwig Kappos8, Fred D. Lublin9, Xavier Montalban, Paul L. O’Connor2, Magnhild Sandberg-Wollheim10, Alan J. Thompson11, Emmanuelle Waubant12, Brian G. Weinshenker13, Jerry S. Wolinsky14 •
University of Amsterdam1, University of Toronto2, Centre Hospitalier Universitaire de Toulouse3, Cleveland Clinic4, Tohoku University5, Charles University in Prague6, University College Dublin7, University of Basel8, Icahn School of Medicine at Mount Sinai9, Lund University10, University College London11, University of California, San Francisco12, Mayo Clinic13, University of Texas Health Science Center at Houston14
01 Feb 2011-Annals of Neurology
TL;DR: These revisions simplify the McDonald Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.
Abstract: New evidence and consensus has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system lesions in space and time has been simplified, and in some circumstances dissemination in space and time can be established by a single scan. These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.

8,883 citations

Journal Article•DOI•
New diagnostic criteria for multiple sclerosis: guidelines for research protocols.

[...]

Charles M. Poser1, Donald W. Paty2, Labe C. Scheinberg3, W I McDonald, F A Davis4, George C. Ebers5, Kenneth P. Johnson6, William A. Sibley7, Donald H. Silberberg8, Wallace W. Tourtellotte9 •
Boston University1, University of British Columbia2, Albert Einstein College of Medicine3, Rush University Medical Center4, University of Western Ontario5, University of Maryland, Baltimore6, University of Arizona7, University of Pennsylvania8, Veterans Health Administration9
01 Mar 1983-Annals of Neurology
TL;DR: Today there is a need for more exact criteria than existed earlier in order to conduct therapeutic trials in multicenter programs, to compare epidemiological surveys, to evaluate new diagnostic procedures, and to estimate the activity of the disease process in MS.
Abstract: Several schemes for the diagnosis and clinical classification of multiple sclerosis (MS) have been advanced [l}. The best known is that published by Schumacher et alC31. The criteria for this scheme were established in order to select patients for participation in therapeutic trials, and pertain only to what might be called definite MS. No provision was made for incorporating supportive laboratory data into the diagnostic criteria. As no reliable specific laboratory test for the diagnosis of MS has been discovered, the diagnosis remains a clinical one, and there is still a need for clinical diagnostic criteria. However, several laboratory and clinical procedures have been developed within the last decade which aid greatly in demonstrating neurological dysfunction attributable to lesions, and even the lesions themselves. One problem with the various published diagnostic classifications is their discrepant terminology: what is considered “probable” in one is called “definite” in another. Another problem is that all the proposed schemes require much subjective judgment, a difficulty which cannot be completely overcome but can be diminished by adding to the clinical evaluation the results of laboratory, neuroimaging, neuropsychological, and neurophysiological procedures. Today there is a need for more exact criteria than existed earlier in order to conduct therapeutic trials in multicenter programs, to compare epidemiological surveys, to evaluate new diagnostic procedures, and to estimate the activity of the disease process in MS. Method and Procedure

7,565 citations

Journal Article•DOI•
International consensus diagnostic criteria for neuromyelitis optica spectrum disorders

[...]

Dean M. Wingerchuk1, Brenda Banwell2, Jeffrey Bennett3, Philippe Cabre, William M. Carroll4, Tanuja Chitnis5, Jérôme De Seze6, Kazuo Fujihara7, Benjamin Greenberg8, Anu Jacob9, Sven Jarius10, Marco Aurélio Lana-Peixoto11, Michael J. Levy12, Jack H. Simon13, Silvia Tenembaum, Anthony Traboulsee14, Patrick Waters15, Kay E. Wellik1, Brian G. Weinshenker1 •
Mayo Clinic1, University of Pennsylvania2, Anschutz Medical Campus3, Sir Charles Gairdner Hospital4, Harvard University5, University of Strasbourg6, Tohoku University7, University of Texas Southwestern Medical Center8, Walton Centre9, Heidelberg University10, Universidade Federal de Minas Gerais11, Johns Hopkins University12, Oregon Health & Science University13, University of British Columbia14, University of Oxford15
14 Jul 2015-Neurology
TL;DR: The International Panel for NMO Diagnosis (IPND) was convened to develop revised diagnostic criteria using systematic literature reviews and electronic surveys to facilitate consensus and achieved consensus on pediatric NMOSD diagnosis and the concepts of monophasicNMOSD and opticospinal MS.
Abstract: Neuromyelitis optica (NMO) is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) that is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). Prior NMO diagnostic criteria required optic nerve and spinal cord involvement but more restricted or more extensive CNS involvement may occur. The International Panel for NMO Diagnosis (IPND) was convened to develop revised diagnostic criteria using systematic literature reviews and electronic surveys to facilitate consensus. The new nomenclature defines the unifying term NMO spectrum disorders (NMOSD), which is stratified further by serologic testing (NMOSD with or without AQP4-IgG). The core clinical characteristics required for patients with NMOSD with AQP4-IgG include clinical syndromes or MRI findings related to optic nerve, spinal cord, area postrema, other brainstem, diencephalic, or cerebral presentations. More stringent clinical criteria, with additional neuroimaging findings, are required for diagnosis of NMOSD without AQP4-IgG or when serologic testing is unavailable. The IPND also proposed validation strategies and achieved consensus on pediatric NMOSD diagnosis and the concepts of monophasic NMOSD and opticospinal MS.

2,945 citations

Journal Article•DOI•
Defining the clinical course of multiple sclerosis: The 2013 revisions

[...]

Fred D. Lublin1, Stephen C. Reingold, Jeffrey A. Cohen2, Gary Cutter3, Per Soelberg Sørensen4, Alan J. Thompson5, Jerry S. Wolinsky6, Laura J. Balcer7, Brenda Banwell8, Frederik Barkhof9, Bruce F. Bebo10, Peter A. Calabresi11, Michel Clanet, Giancarlo Comi12, Robert J. Fox2, Mark S. Freedman13, Andrew D. Goodman14, Matilde Inglese1, Ludwig Kappos15, Bernd C. Kieseier16, John A. Lincoln6, Catherine Lubetzki17, Aaron E. Miller1, Xavier Montalban18, Paul O'Connor19, John Petkau20, Carlo Pozzilli21, Richard A. Rudick2, Maria Pia Sormani, Olaf Stüve22, Emmanuelle Waubant23, Chris H. Polman9 •
Icahn School of Medicine at Mount Sinai1, Cleveland Clinic2, University of Alabama at Birmingham3, University of Copenhagen4, University College London5, University of Texas Health Science Center at Houston6, New York University7, University of Pennsylvania8, VU University Amsterdam9, National Multiple Sclerosis Society10, Johns Hopkins University11, Vita-Salute San Raffaele University12, University of Ottawa13, University of Rochester14, University of Basel15, University of Düsseldorf16, Pierre-and-Marie-Curie University17, Autonomous University of Barcelona18, University of Toronto19, University of British Columbia20, Sapienza University of Rome21, University of Texas Southwestern Medical Center22, University of California, San Francisco23
15 Jul 2014-Neurology
TL;DR: Refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression are proposed and strategies for future research to better define phenotypes are outlined.
Abstract: Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined.

2,180 citations

Journal Article•DOI•
International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions

[...]

Lauren B. Krupp1, Marc Tardieu, Maria Pia Amato2, Brenda Banwell3, Tanuja Chitnis4, Russell C. Dale5, Angelo Ghezzi, Rogier Q. Hintzen6, Andrew J. Kornberg7, Daniela Pohl8, Kevin Rostasy, Silvia Tenembaum, Evangeline Wassmer9 •
Stony Brook University1, University of Florence2, Children's Hospital of Philadelphia3, Harvard University4, University of Sydney5, Erasmus University Rotterdam6, Royal Children's Hospital7, Children's Hospital of Eastern Ontario8, Boston Children's Hospital9
09 Apr 2013-Multiple Sclerosis Journal
TL;DR: Revised criteria are proposed for pediatric acute disseminated encephalomyelitis, pediatric clinically isolated syndrome, pediatric neuromyELitis optica and pediatric MS to incorporate advances in delineating the clinical and neuroradiologic features of these disorders.
Abstract: Background: There has been tremendous growth in research in pediatric multiple sclerosis (MS) and immune mediated central nervous system demyelinating disorders since operational definitions for these conditions were first proposed in 2007. Further, the International Pediatric Multiple Sclerosis Study Group (IPMSSG), which proposed the criteria, has expanded substantially in membership and in its international scope. Objective: The purpose of this review is to revise the 2007 definitions in order to incorporate advances in delineating the clinical and neuroradiologic features of these disorders. Methods: Through a consensus process, in which input was sought from the 150 members of the Study Group, criteria were drafted, revised and finalized. Final approval was sought through a web survey. Results: Revised criteria are proposed for pediatric acute disseminated encephalomyelitis, pediatric clinically isolated syndrome, pediatric neuromyelitis optica and pediatric MS. These criteria were approved by 93% or more of the 56 Study Group members who responded to the final survey. Conclusions: These definitions are proposed for clinical and research purposes. Their utility will depend on the outcomes of their application in prospective research.

830 citations

Related Papers (5)
Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

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21 Dec 2017-Lancet Neurology
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Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria

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01 Feb 2011-Annals of Neurology
Chris H. Polman, Stephen C. Reingold, Brenda Banwell, Michel Clanet, Jeffrey A. Cohen, Massimo Filippi, Kazuo Fujihara, Eva Havrdova, Michael Hutchinson, Ludwig Kappos, Fred D. Lublin, Xavier Montalban, Paul L. O’Connor, Magnhild Sandberg-Wollheim, Alan J. Thompson, Emmanuelle Waubant, Brian G. Weinshenker, Jerry S. Wolinsky 
Defining the clinical course of multiple sclerosis: The 2013 revisions

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15 Jul 2014-Neurology
Fred D. Lublin, Stephen C. Reingold, Jeffrey A. Cohen, Gary Cutter, Per Soelberg Sørensen, Alan J. Thompson, Jerry S. Wolinsky, Laura J. Balcer, Brenda Banwell, Frederik Barkhof, Bruce F. Bebo, Peter A. Calabresi, Michel Clanet, Giancarlo Comi, Robert J. Fox, Mark S. Freedman, Andrew D. Goodman, Matilde Inglese, Ludwig Kappos, Bernd C. Kieseier, John A. Lincoln, Catherine Lubetzki, Aaron E. Miller, Xavier Montalban, Paul O'Connor, John Petkau, Carlo Pozzilli, Richard A. Rudick, Maria Pia Sormani, Olaf Stüve, Emmanuelle Waubant, Chris H. Polman 
Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the Diagnosis of Multiple Sclerosis

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Frequently Asked Questions (2)
Q1. What contributions have the authors mentioned in the paper "The diagnosis of multiple sclerosis (ms) is based on typical neurological symptoms and signs along with evidence of dissemination of central nervous system (cns) lesions in space" ?

A review of the diagnosis of MS including the approach to investigating patients with suspected MS, the diagnostic criteria for MS and their application in clinical practice can be found in this paper. 

Magnetic resonance imaging (MRI) is often sufficient to confirm the diagnosis when characteristic lesions of MS accompany a typical clinical syndrome, but in some patients, further supportive information can be obtained from cerebrospinal fluid examination and neurophysiological testing. 

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What are the challenges in nsclc diagnosis?

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