Cited by 701Multiple Sclerosis Research StudiesPeripheral Neuropathies and DisordersClinical Reasoning and Diagnostic Skills

The DOI matches its Crossref record; 85 of the 85 references it cites were found in a registry or an index; 65 of the 151 sources its claims cite were checked for support.

Diagnosis of multiple sclerosis: progress and challenges

Open access

Abstract

The diagnosis of multiple sclerosis is based on neurological symptoms and signs, alongside evidence of dissemination of CNS lesions in space and time. MRI is often sufficient to confirm the diagnosis when characteristic lesions accompany a typical clinical syndrome, but in some patients, further supportive information is obtained from cerebrospinal fluid examination and neurophysiological testing. Differentiation is important from other diseases in which demyelination is a feature (eg, neuromyelitis optica spectrum disorder and acute disseminated encephalomyelitis) and from non-demyelinating disorders such as chronic small vessel disease and other inflammatory, granulomatous, infective, metabolic, and genetic causes that can mimic multiple sclerosis. Advances in MRI and serological and genetic testing have greatly increased accuracy in distinguishing multiple sclerosis from these disorders, but misdiagnosis can occur. In this Series paper we explore the progress and challenges in the diagnosis of multiple sclerosis with reference to diagnostic criteria, important differential diagnoses, controversies and uncertainties, and future prospects.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This review summarizes progress and challenges in diagnosing multiple sclerosis, emphasizing McDonald 2010 clinical/MRI criteria, differential diagnosis, and emerging biomarkers. It highlights that MRI enables earlier diagnosis but can be misapplied, with misdiagnosis rates as high as 10% and several unresolved controversies.

Key findings

  • MS diagnosis requires objective evidence of CNS lesions disseminated in time and space; McDonald 2010 criteria allow a diagnosis of RRMS in up to one third of clinically isolated syndrome patients with a single MRI, and MRI is abnormal in virtually all patients with established MS and over 80% of CIS patients who develop MS.
  • RRMS accounts for 85–90% of patients, with mean age at onset 30 years and women affected three times as commonly as men; PPMS accounts for 10–15%, with mean age at onset 40 years and no gender bias. Spinal cord lesions occur in 80–90% of established MS and up to half of CIS patients, while CSF oligoclonal bands are found in up to 90% of people with MS but less than 20% of NMOSD patients.
  • Differential diagnosis includes NMOSD, ADEM, and non-demyelinating mimics; NMOSD is approximately 100 times less common than MS in European and North American populations, about 70% of relapsing NMOSD patients are AQP4-IgG positive, and NMOSD shows a female:male ratio up to 9:1 with mean age at onset 39 years. Misdiagnosis rates may be as high as 10%, with common misdiagnosed disorders including small-vessel cerebrovascular disease, migraine, fibromyalgia, and functional neurological disorders.
  • A third of radiologically isolated syndrome patients develop clinical symptoms within the first 5 years; 30–60% of patients presenting with atypical demyelinating lesions develop MS; up to 5% of people with MS develop first symptoms in childhood. Future directions include MAGNIMS-proposed modifications, cortical lesions, the central vein sign, novel CSF/body fluid biomarkers, and optical coherence tomography.

Methods

  • Narrative review with a literature search of MEDLINE from 01 January 1995 to 15 May 2016 using the terms “multiple sclerosis”, “neuromyelitis optica”, “acute disseminated encephalomyelitis”, “diagnosis”, “diagnostic criteria”, and “differential diagnosis” for English-language articles; additional articles were sought from reference lists, with priority given to new studies published in the last 5 years.
  • No primary data collection or formal meta-analysis; the paper synthesizes diagnostic criteria, important differential diagnoses, current controversies and uncertainties, and future prospects.

Limitations

  • Paper states: McDonald MRI criteria are intended for patients in whom MS is clinically suspected, not to differentiate MS from other neurological disorders; the criteria have not been investigated in patients older than 50 years; misdiagnosis can occur (rates as high as 10%); the roles of spinal cord imaging and CSF examination remain controversial; and gadolinium safety concerns are under regulatory review.
  • Evident from the text: this is a narrative review with expert-selected literature and consensus recommendations rather than a systematic review, and the search was limited to MEDLINE, English-language articles, and the period 1995–2016, so other evidence may be missed.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/s0140-6736(16)30959-x

Cites

85 of 85 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

49 No full text of the sources · 30 Supported · 21 Partly supported · 18 No basis given · 10 Own interpretation · 6 Supported so far · 4 Own method · 3 Sources not found · 1 Not checked yet · accuracy not yet measured

Show all 51 claims

  • It may state two separate claims as one. 70
  • Probably not a substantial claim. 34
91 of 91
  • The paper relies on this without support.

    Effective treatments for RRMS exist.

    “An early and accurate diagnosis of MS is essential because there are now effective treatments for RRMS.”
  • The paper relies on this without support.

    The McDonald 2010 criteria are the current diagnostic criteria for MS.

    “The current diagnostic criteria for MS, the McDonald 2010 criteria, are shown in Panel 1.”
  • The paper relies on this without support.

    The diagnosis of MS requires objective evidence of CNS lesions disseminated in time and space.

    “The diagnosis of MS requires objective evidence of CNS lesions disseminated in time and space.”
  • The paper relies on this without support.

    The diagnosis of MS and its many differential diagnoses can still be challenging.

    “The diagnosis of MS and its many differential diagnoses can still be challenging but progress continues to be made.”
  • The paper relies on this without support.

    Diagnostic criteria for both MS and NMOSD have changed in recent years as new pathological, immunological, imaging, clinical and therapeutic findings have emerged.

    “Diagnostic criteria for both MS and NMOSD have changed in recent years as new pathological, immunological, imaging, clinical and therapeutic findings have emerged.”
5 of 5

Citations

Cites

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Cited by

Sorted by citations

Items 401–500 of 701

Metadata

Authors
Brownlee, W. J., Hardy, T. A., Fazekas, F., & Miller, D. H.
Affiliations
  • National Hospital for Neurology and Neurosurgery (GB)
  • The University of Sydney (AU)
  • Medical University of Graz (AT)
  • National Institute for Health and Care Research (GB)
Corresponding author
Brownlee, Wallace J
Venue
The Lancet
Publisher
Elsevier BV
Published
2017-04
Volume
389
Issue
10076
Pages
1336-1346
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
OpenAlex
W2553410079
Cited by
701
References
81
Citations by year
2026: 53 · 2025: 73 · 2024: 79 · 2023: 101 · 2022: 73 · 2021: 93 · 2020: 88 · 2019: 68 · 2018: 52 · 2017: 20
FWCI
36.44
Type
journal article
Language
en
Open access
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • National Institute for Health and Care Research (NF-SI-0508-10058)
  • Multiple Sclerosis Society
  • University College London Hospitals NHS Foundation Trust
Topics
  • Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Clinical Neurology › Peripheral Neuropathies and Disorders
  • Health Sciences › Medicine › Family Practice › Clinical Reasoning and Diagnostic Skills
Keywords
multiple sclerosis, diagnosis, diagnostic criteria, magnetic resonance imaging, cerebrospinal fluid analysis, neurophysiological assessment, demyelination, neuromyelitis optica spectrum disorder, acute disseminated encephalomyelitis, differential diagnosis, misdiagnosis, serological testing, genetic testing, cerebral small vessel disease
MeSH terms
Brain, Diagnosis, Differential, Encephalomyelitis, Acute Disseminated, Humans, Magnetic Resonance Imaging, Multiple Sclerosis, Neuromyelitis Optica, Spinal Cord, Multiple Sclerosis, Relapsing-Remitting

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