Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

TLDR: 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.

Figures

Table 1: The 2017 McDonald Criteria for diagnosis of multiple sclerosis in patients with an attacka at onset

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THELANCETNEUROLOGY-D-17-00665 revision 1
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Diagnosis of Multiple Sclerosis: 2017 Revisions of the “McDonald” Criteria
Alan J Thompson, Brenda L Banwell, Frederik Barkhof, William M Carroll, Timothy Coetzee,
Giancarlo Comi, Jorge Correale, Franz Fazekas, Massimo Filippi, Mark S Freedman, Kazuo
Fujihara, Steven L Galetta, Hans Peter Hartung, Ludwig Kappos, Fred D Lublin, Ruth Ann
Marrie, Aaron E Miller, David H Miller, Xavier Montalban, Ellen M Mowry, Per Soelberg-
Sorensen, Mar Tintoré, Anthony L Traboulsee, Maria Trojano, Bernard MJ Uitdehaag, Sandra
Vukusic, Emmanuelle Waubant, Brian G Weinshenker, Stephen C Reingold, Jeffrey A Cohen
Faculty of Brain Sciences, University College London, London, UK (Prof AJ Thompson MD)
Division of Neurology, Children’s Hospital of Philadelphia, Perelman School of Medicine,
University of Pennsylvania, Philadelphia, PA, USA (Prof BL Banwell MD)
Radiology & Nuclear Medicine Department, VU Medical Center, Amsterdam, The Netherlands
and Institutes of Neurology and Healthcare Engineering, University College London, London,
UK (Prof F Barkhof MD)
Neurology Department, Sir Charles Gairdner Hospital, Perth, Australia (Prof WM Carroll MD)
National Multiple Sclerosis Society, New York, NY, USA (T Coetzee PhD)
Department of Neurology, Vita-Salute San Raffaele University-Ospedale San Raffaele, Milan,
Italy (Prof G Comi MD)
Institute for Neurological Research Dr. Raúl Carrea, FLENI, Buenos Aires, Argentina (Prof JD
Correale MD)
Department of Neurology, Medical University of Graz, Graz, Austria (Prof F Fazekas MD)
The Neuroimaging Research Unit (NRU), San Raffaele Scientific Institute, Vita-Salute San
Raffaele University, Milan, Italy (Prof M Filippi MD, FEAN)
Department of Medicine, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa,
ON, Canada (Prof MS Freedman MD)

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Department of Multiple Sclerosis Therapeutics, Fukushima Medical University School of
Medicine and Multiple Sclerosis & Neuromyelitis Optica Center, Southern TOHOKU Research
Institute for Neuroscience, Koriyama, Fukushima, Japan (Prof K Fujihara MD)
Department of Neurology, New York University Langone Medical Center, New York, NY, USA
(Prof SL Galetta MD)
Department of Neurology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany
(Prof. HP Hartung MD)
Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine and
Biomedical Engineering, University Hospital and University of Basel, Basel, Switzerland (Prof L
Kappos MD)
Corinne Goldsmith Dickinson Center for MS, Icahn School of Medicine at Mount Sinai, New
York, NY, USA (Prof. FD Lublin MD, Prof AE Miller MD)
Departments of Internal Medicine and Community Health Sciences, Rady Faculty of Health
Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada (Prof
RA Marrie MD, PhD)
Queen Square MS Centre, Institute of Neurology, University College London, London, UK (Prof
DH Miller MD)
Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Vall d’Hebron University Hospital, Barcelona,
Spain (Prof X Montalban MD, M Tintoré MD) and Division of Neurology, University of Toronto,
St Michael’s Hospital, Toronto, Canada (Prof X Montalban)
Department of Neurology, Johns Hopkins University, Baltimore, MD, USA (EM Mowry MD)
Danish Multiple Sclerosis Center, University of Copenhagen, Rigshospitalet, Copenhagen,
Denmark (Prof P Soelberg Sorensen, MD)
Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC,
Canada (AL Traboulsee MD)

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Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari,
Bari, Italy (Prof M Trojano MD)
Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands (Prof
BMJ Uitdehaag MD)
Service de Neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation,
Hôpital Neurologique, Hospices Civils de Lyon, Bron, France; Centre des Neurosciences de
Lyon, INSERM 1028 et CNRS UMR5292, Lyon, France; Université Claude Bernard Lyon 1,
Faculté de Médecine Lyon-Est, Villeurbanne, Auvergne-Rhône-Alpes, France (Prof S Vukusic
MD)
Department of Neurology, University of California at San Francisco, San Francisco, CA, USA
(Prof E Waubant, MD)
Department of Neurology, Mayo Clinic, Rochester, MN, USA (Prof BG Weinshenker MD)
Scientific & Clinical Review Associates LLC, Salisbury, CT, USA (SC Reingold, PhD)
Neurologic Institute, Cleveland Clinic, Cleveland, OH, USA (Prof JA Cohen MD)
Correspondence to:
Prof Jeffrey A Cohen, Neurologic Institute, Cleveland Clinic, Cleveland, OH 44195 USA
cohenj@ccf.org
Title character count: 74 (with spaces)
Abstract word count: 187 (150 maximum)
Word count: 4598 (4500 maximum)
References 99 (100 maximum)
Tables: 1
Panels 6
Figures: 0

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Abstract
The 2010 McDonald criteria for diagnosis of multiple sclerosis (MS) are widely used in research
and clinical practice. Scientific advances in the past seven years suggest that they may 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 (CIS), define what is needed to fulfill
dissemination in time and space, and stress the need for no better explanation for the
presentation. The following changes were made: in patients with a typical CIS and clinical or
MRI demonstration of dissemination in space, the presence of cerebrospinal-fluid-specific
oligoclonal bands allows an MS diagnosis; symptomatic lesions can be used to demonstrate
dissemination in space and/or time in patients with supratentorial, infratentorial, or spinal cord
syndrome; and cortical lesions can be used to demonstrate dissemination in space.
Recommended research to further refine the criteria includes (i) inclusion of optic nerve
involvement; (ii) validation in diverse populations; and (iii) incorporation of advanced imaging,
neurophysiological, and body fluid markers.

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Introduction
Diagnostic criteria for multiple sclerosis (MS) have evolved over time, with the most recent
recommendations from the International Panel on Diagnosis of MS (the Panel) appearing more
than six years ago.
1-5
The increasing incorporation of paraclinical assessments, especially
imaging, to supplement clinical findings has allowed earlier, more sensitive, and more specific
diagnosis.
6
New data, emerging technology, and evolving consensus necessitate a periodic re-
examination of diagnostic criteria and their utility. The Panel reconvened under the auspices of
the International Advisory Committee on Clinical Trials in MS (sponsored by the U.S. National
MS Society and the European Committee for Treatment and Research in MS) for two meetings
(November 2-5, 2016, Philadelphia and May 20-21, 2017, Berlin). Herein, we discuss issues
related to misdiagnosis, differential diagnosis, and appropriate application of the McDonald
(International) Criteria, with a particular emphasis on diagnosis in diverse populations and in
patients with atypical presentations. We present recommendations concerning the MS
diagnostic process, recommend specific revisions to the McDonald Criteria, and outline future
research to refine the McDonald Criteria.
Conduct of the Panel meetings and considerations related to the 2017 revisions to the
McDonald Criteria
Convening the Panel meetings was motivated by new data concerning (i) the performance of
the 2010 McDonald Criteria in diverse populations; (ii) the relationship between MS and other
diseases with potentially overlapping clinical and imaging features such as is seen in
neuromyelitis optica spectrum disorders (NMOSD); (iii) challenges in making the diagnosis in
individuals with non-classical presentations; (iv) the frequency and consequences of
misdiagnosis; and (v) cerebrospinal fluid (CSF) and other paraclinical tests related to diagnosis

Frequently asked questions

Q1. What contributions have the authors mentioned in the paper "Diagnosis of multiple sclerosis: 2017 revisions of the “mcdonald” criteria" ?

The most recent version of the McDonald Criteria was proposed by Thompson et al. this paper, with a particular emphasis on diagnosis in diverse populations and patients with atypical presentations. 

Q2. What future works have the authors mentioned in the paper "Diagnosis of multiple sclerosis: 2017 revisions of the “mcdonald” criteria" ?

It was recognized that application of new diagnostic criteria can have an impact on future recruitment into and interpretation of clinical trials and observational studies98 but should not affect registration of already-approved medications. The goal is to make a rapid and accurate diagnosis of MS, keeping fully in mind the potential dangers of misdiagnosis in an era with increasing numbers of treatment options for MS, which carry varying degrees of risk. The importance of correct diagnosis is further heightened by the observation that certain MS DMTs are contraindicated in some of the more common differential diagnoses, for example, NMOSD. It reviewed papers on topics including, but not limited to, the role in diagnosis of magnetic resonance imaging, optical coherence tomography, evoked potentials, and cerebrospinal fluid analysis ; of diagnosis in diverse populations ( pediatric, Asian, and Latin American ) ; in patients with non-classical presentations ( e. g. radiologically isolated syndrome and solitary sclerosis ) ; of differential diagnosis between multiple sclerosis, neuromyelitis spectrum disorders, and other neurological disorders ; and the intersection of diagnosis with disease phenotype designation. 

Q3. What is the role of a MRI in diagnosing MS?

With the growing interest in precision medicine and rapidly evolving technologies, it will be critical that the community develop an approach to validation of all paraclinical tests for MS diagnosis and incorporation into practice when appropriate. 

Q4. What is the importance of OCBs in MS?

Presence of CSF oligoclonal bands allows the diagnosis of MS in selected patients Multiple studies provide evidence that in adult patients with CIS, CSF OCBs are an independent predictor of the risk of a second attack when controlling for demographic, clinical, treatment, and MRI variables. 

Q5. What changes to the McDonald Criteria were made?

The proposed 2017 revisions to the well established McDonald Criteria go beyond prior versions by revitalizing the role of CSF analysis, by reconsidering the value of imaging findings previously not included, such as symptomatic and cortical lesions, and by articulating more clearly cautions about misdiagnosis and differential diagnosis, all of which were supported by a sound evidence base. 

Q6. What is the role of MRI in MS?

MAGNIMS and the Consortium of MS Centers recently proposed standardized MRI protocols for the diagnostic process, to determine prognosis, and for follow-up.54-56 Brain and spinal cord MRI remain the most useful paraclinical tests to aid the diagnosis of MS and can substitute for clinical findings in determination of dissemination in space (DIS) and/or time (DIT) in patients with a typical CIS. 

Q7. What is the role of higher field strength imaging in MS diagnosis?

The role of higher field strength imaging requires detailed investigation to determine if it is useful and practical, particularly in non-academic settings, given its improved ability to detect lesions and reveal their anatomic features. 

Q8. What are the key proposals that require further evidence if they are to be adopted into diagnostic criteria?

Key proposals that require further evidence if they are to be adopted into diagnostic criteriaThe 2001 and 2005 McDonald Criteria required three or more periventricular lesions as one of the anatomic locations that could fulfill MRI criteria for DIS.3,4 

Q9. What is the importance of OCBs in diagnosing MS?

While negative CSF OCBs does not rule out MS, particularly early in the condition and in children,58,59 caution should be exercised in diagnosing MS when CSF OCBs are not detected and, certainly, in the presence of atypical clinical, imaging, or CSF findings. 

Q10. What did the Panel find to be the significant improvement in sensitivity?

The recent MAGNIMS analysis showed that adding optic nerve involvement detected by MRI or VEP as a fifth anatomic site led to a minor improvement in sensitivity from 0.88 to 0.91 but substantially reduced specificity from 0.52 from 0.41.72 

Q11. What factors predict the risk of subsequent MS diagnosis?

The factors predicting increased risk of subsequent MS diagnosis are similar to those predicting MS diagnosis after a CIS: younger age, higher cerebral lesion load, asymptomatic infratentorial or spinal cord lesions, gadolinium-enhancing lesions, presence of CSF OCBs, and abnormal VEP.87,89Some Panel members argued that individuals with RIS have a high likelihood of havingMS and may already exhibit evidence of putative MS pathobiology, including fatigue,90 cognitive impairment,91 and thalamic atrophy,92 and that postponing an MS diagnosis and initiation of DMT might increase the risk of disability. 

Q12. What are the issues related to the 2010 McDonald Criteria?

the authors discuss issues related to misdiagnosis, differential diagnosis, and appropriate application of the McDonald (International) Criteria, with a particular emphasis on diagnosis in diverse populations and in patients with atypical presentations. 

Q13. What criteria should be excluded from the diagnosis of MS?

The Panel agreed that the McDonald Criteria should not be applied to children at the time of ADEM presentation and that occurrence of a subsequent attack characteristic of MS is necessary to diagnose MS.38 Alternative diagnoses, including NMOSD, need to be excluded in all children in whom the diagnosis of MS is being considered.