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Cited by 642Multiple Sclerosis Research StudiesClinical Reasoning and Diagnostic SkillsPeripheral Neuropathies and Disorders

Differential diagnosis of suspected multiple sclerosis: a consensus approach

Open access
Miller, DH, Weinshenker, BG, Filippi, M, Banwell, BL, Cohen, JA, Freedman, MS, Galetta, SL, Hutchinson, M, Johnson, RT, Kappos, L, Kira, J, Lublin, FD, McFarland, HF, Montalban, X, Panitch, H, Richert, JR, Reingold, SC, Polman, CH·2008·Multiple Sclerosis Journal
DOI 10.1177/1352458508096878PMC PMC2850590
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Abstract

Background and objectives Diagnosis of multiple sclerosis (MS) requires exclusion of diseases that could better explain the clinical and paraclinical findings. A systematic process for exclusion of alternative diagnoses has not been defined. An International Panel of MS experts developed consensus perspectives on MS differential diagnosis. Methods Using available literature and consensus, we developed guidelines for MS differential diagnosis, focusing on exclusion of potential MS mimics, diagnosis of common initial isolated clinical syndromes, and differentiating between MS and non-MS idiopathic inflammatory demyelinating diseases. Results We present recommendations for 1) clinical and paraclinical red flags suggesting alternative diagnoses to MS; 2) more precise definition of “clinically isolated syndromes” (CIS), often the first presentations of MS or its alternatives; 3) algorithms for diagnosis of three common CISs related to MS in the optic nerves, brainstem, and spinal cord; and 4) a classification scheme and diagnosis criteria for idiopathic inflammatory demyelinating disorders of the central nervous system. Conclusions Differential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision.

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  • 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 of MS is broad and many neurologists use the approach of identifying”

    From Diagnosis of multiple sclerosis: progress and challenges (2017) · cites this paper as [42]

    The Discussion/conclusions says the range of diseases to exclude in MS diagnosis is wide, and Methods > Exclusion of diagnostic alternatives describes clinical, imaging, and laboratory red flags that point away from MS. The paper presents this as a consensus approach, but does not establish that many neurologists use it in practice; no page numbers are available in our copy. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Misdiagnosis of MS remains an issue in clinical practice.

    “Misdiagnosis of MS remains an issue in clinical practice. 8-11”

    From Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria (2018) · cites this paper as [9]

  • MS must be differentiated from other diseases in which demyelination is a feature, such as NMOSD and ADEM, and from non-demyelinating conditions such as chronic small vessel disease and other inflammatory, granulomatous, infective, metabolic and genetic causes that can mimic MS.

    “It is important to differentiate MS not only from other diseases in which demyelination is a feature e.g.neuromyelitis spectrum disorder (NMOSD) and acute disseminated encephalomyelitis (ADEM), but also non-demyelinating conditions such as chronic small vessel disease and other inflammatory, granulomatous, infective, metabolic and genetic causes that can mimic MS.”

    From Diagnosis of multiple sclerosis: progress and challenges (2017) · cites this paper as [42]

  • MRI findings in ADEM include large (>1-2cm), bilateral white matter lesions and deep grey matter lesions and contrast enhancement.

    “MRI findings include large (>1-2cm), bilateral white matter lesions and deep grey matter lesions and contrast enhancement.42”

    From Diagnosis of multiple sclerosis: progress and challenges (2017) · cites this paper as [42]

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Cited by

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Authors
Miller, D., Weinshenker, B., Filippi, M., Banwell, B., Cohen, J., Freedman, M., Galetta, S., Hutchinson, M., Johnson, R., Kappos, L., Kira, J., Lublin, F., McFarland, H., Montalban, X., Panitch, H., Richert, Jr., Reingold, S., & Polman, C.
Affiliations
  • UCL Queen Square Institute of Neurology (GB)
  • Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
  • IRCCS Ospedale San Raffaele (IT)
  • The Hospital for Sick Children, Department of Paediatrics, Division of Neurology, Toronto, California, USA
  • The Mellen Center, Cleveland Clinic, Cleveland, Ohio, USA
  • University of Ottawa (CA)
  • Department of Neurology, University of Pennsylvania Hospital, Philadelphia, Pennsylvania, USA
  • University College Dublin (IE)
  • Johns Hopkins University (US)
  • University Hospital of Basel (CH)
  • Kyushu University (JP)
  • Icahn School of Medicine at Mount Sinai (US)
  • National Institutes of Health (US)
  • Unitat de Neuroimmunologia Clinica, Hospital Universitari Vall d’Hebron, Barcelona, Spain
  • University of Vermont (US)
  • National Multiple Sclerosis Society (US)
  • 16 Research and Clinical Programs Department, National Multiple Sclerosis Society, New York City, New York, USA; 17 Scientific and Clinical Review Associates, LLC, New York City, New York, USA
  • 18 Department of Neuroinflammation, Institute of Neurology, University College London, UK
ORCID
Venue
Multiple Sclerosis Journal
Publisher
SAGE Publications
Published
2008-09-19
Volume
14
Issue
9
Pages
1157-1174
ISSN
  • 1352-4585 (ISSN-L)
  • 1477-0970
DOI
10.1177/1352458508096878
PMC
PMC2850590
OpenAlex
W2135440918
Cited by
642
References
1
Citations by year
2026: 5 · 2025: 22 · 2024: 17 · 2023: 29 · 2022: 23 · 2021: 27 · 2020: 27 · 2019: 39 · 2018: 44 · 2017: 50 · 2016: 32 · 2015: 54 · 2014: 52 · 2013: 55 · 2012: 66
FWCI
23.73
Type
journal article
Language
en
Open access
Licence
Locations
  • Multiple Sclerosis Journal (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
  • Pure Amsterdam UMC (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Funders
Multiple Sclerosis Society
Topics
  • Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Family Practice › Clinical Reasoning and Diagnostic Skills
  • Health Sciences › Medicine › Clinical Neurology › Peripheral Neuropathies and Disorders
Keywords
multiple sclerosis, differential diagnosis, clinically isolated syndrome, optic neuritis, brainstem syndrome, spinal cord syndromes, diagnostic criteria, consensus recommendations
MeSH terms
Algorithms, Diagnosis, Differential, Humans, Multiple Sclerosis, Practice Guidelines as Topic

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