Cited by 334Multiple Sclerosis Research StudiesClinical Reasoning and Diagnostic SkillsPeripheral Neuropathies and Disorders

The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index; none of the 21 sources its claims cite is checked for support yet.

The contemporary spectrum of multiple sclerosis misdiagnosis

Open access

Abstract

OBJECTIVE: To characterize patients misdiagnosed with multiple sclerosis (MS). METHODS: Neurologists at 4 academic MS centers submitted data on patients determined to have been misdiagnosed with MS. RESULTS: Of 110 misdiagnosed patients, 51 (46%) were classified as "definite" and 59 (54%) "probable" misdiagnoses according to study definitions. Alternate diagnoses included migraine alone or in combination with other diagnoses 24 (22%), fibromyalgia 16 (15%), nonspecific or nonlocalizing neurologic symptoms with abnormal MRI 13 (12%), conversion or psychogenic disorders 12 (11%), and neuromyelitis optica spectrum disorder 7 (6%). Duration of misdiagnosis was 10 years or longer in 36 (33%) and an earlier opportunity to make a correct diagnosis was identified for 79 patients (72%). Seventy-seven (70%) received disease-modifying therapy and 34 (31%) experienced unnecessary morbidity because of misdiagnosis. Four (4%) participated in a research study of an MS therapy. Leading factors contributing to misdiagnosis were consideration of symptoms atypical for demyelinating disease, lack of corroborative objective evidence of a CNS lesion as satisfying criteria for MS attacks, and overreliance on MRI abnormalities in patients with nonspecific neurologic symptoms. CONCLUSIONS: Misdiagnosis of MS leads to unnecessary and potentially harmful risks to patients. Misinterpretation and misapplication of MS clinical and radiographic diagnostic criteria are important contemporary contributors to misdiagnosis.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

In a 4-center study, 110 patients previously diagnosed with MS were determined by MS specialists to have been misdiagnosed; common alternative diagnoses were migraine, fibromyalgia, nonspecific neurologic symptoms with abnormal MRI, conversion/psychogenic disorders, and NMOSD. Misdiagnosis was often prolonged, frequently led to unnecessary disease-modifying therapy, and was commonly attributed to misapplication of clinical and radiographic MS diagnostic criteria.

Key findings

  • Of 110 misdiagnosed patients, 51 (46%) were classified as “definite” and 59 (54%) as “probable” misdiagnoses; 93 (85%) were women, mean age was 49 ± 11 years.
  • The most frequent alternative diagnoses were migraine alone or in combination (24, 22%), fibromyalgia (16, 15%), nonspecific or nonlocalizing neurologic symptoms with abnormal MRI (13, 12%), conversion or psychogenic disorder (12, 11%), and NMOSD (7, 6%).
  • Misdiagnosis lasted 10 years or longer in 36 patients (33%); an earlier missed opportunity for correct diagnosis was identified in 79 (72%); 77 (70%) received disease-modifying therapy, and 34 (31%) experienced unnecessary morbidity. Four patients (4%) participated in a research study of an MS therapy.
  • Leading contributors were consideration of symptoms atypical for demyelinating disease (72, 65%), lack of corroborative objective evidence of a CNS lesion for historical attacks (53, 48%), and overreliance on MRI abnormalities in patients with nonspecific neurologic symptoms (66, 60%).

Methods

  • Twenty-three neurologists with MS subspecialty training/practice focus at 4 US academic MS centers (University of Vermont, Oregon Health & Science University, Washington University, Mayo Clinic) submitted data on patients determined to have been misdiagnosed with MS.
  • Patients were identified prospectively during 13 months or shortly before study initiation; data were collected August 1, 2014, to September 1, 2015. Inclusion required prior diagnosis of MS by another physician; patients for whom MS was only being considered but not firmly diagnosed were excluded.
  • “Definite misdiagnosis” required a definitively made alternative diagnosis based on clinical, laboratory, and neuroimaging evaluation; “probable misdiagnosis” required a suspected alternative diagnosis and failure to meet MS diagnostic criteria. Data were entered via a REDCap web form; neurologists also assessed whether inappropriate application of clinical or radiographic MS diagnostic criteria contributed to misdiagnosis.

Limitations

  • Stated: participating neurologists may have been incorrect in assessing misdiagnosis; lack of specific biomarkers for the disorders mistaken for MS means experts might disagree on the correct diagnosis; selection and referral bias likely influenced patient characteristics; no frequency estimate of MS misdiagnosis was obtained; contributor assessments may be speculative because neurologists usually did not make the initial incorrect MS diagnosis; hindsight bias may have influenced opinions about earlier missed opportunities.
  • Evident from the design: the study reports a referred/academic-center case series without a population denominator, so it cannot establish incidence or prevalence of misdiagnosis; data were collected by treating neurologists using a non-identifiable web form, and no independent adjudication or validation of alternative diagnoses is described.

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Integrity signals

Registry

Crossref · 10.1212/wnl.0000000000003152

Cites

34 of 34 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

29 Own result · 13 Sources not found · 13 Own interpretation · 6 Own method · 2 No basis given

Show all 38 claims

  • It may state two separate claims as one. 18
  • Probably not a substantial claim. 10
  • The quote only partly states this claim. 2
25 of 25
  • The paper relies on this without support.

    The participating MS specialists accurately determined that the patients had been misdiagnosed with MS.

    “Neurologists participating in the study may have been incorrect in their assessment of misdiagnosis in some cases.”
  • The paper relies on this without support.

    The alternative diagnoses assigned by participating neurologists are correct.

    “Given the lack of specific biomarkers for the disorders mistaken for MS identified in this study, it is possible that neurologists might disagree on their assessment of the correct clinical diagnosis in some cases.”
  • The paper relies on this without support.

    The reported morbidities were caused by the MS misdiagnosis.

    “34 (31%) experienced “unnecessary morbidity as a direct result of a misdiagnosis of MS.””
  • The paper relies on this without support.

    The contributors to misdiagnosis identified by participating neurologists are valid.

    “in most instances, our neurologists did not participate in making the initial incorrect diagnosis of MS and thus their assessment of potential contributors to misdiagnosis may be considered speculative.”
  • The paper relies on this without support.

    Natalizumab is associated with progressive multifocal leukoencephalopathy.

    “Fourteen patients received natalizumab, a drug associated with progressive multifocal leukoencephalopathy.”
5 of 5

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Metadata

Authors
Solomon, A. J., Bourdette, D. N., Cross, A. H., Applebee, A., Skidd, P. M., Howard, D. B., Spain, R. I., Cameron, M. H., Kim, E., Mass, M. K., Yadav, V., Whitham, R. H., Longbrake, E. E., Naismith, R. T., Wu, G. F., Parks, B. J., Wingerchuk, D. M., Rabin, B. L., Toledano, M., Tobin, W. O., Kantarci, O. H., Carter, J. L., Keegan, B. M., & Weinshenker, B. G.
Affiliations
University of Vermont (US)
Venue
Neurology
Published
2016-09-27
Volume
87
Issue
13
Pages
1393-1399
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
OpenAlex
W2517920154
Cited by
334
References
30
Citations by year
2026: 28 · 2025: 34 · 2024: 39 · 2023: 29 · 2022: 40 · 2021: 34 · 2020: 40 · 2019: 32 · 2018: 34 · 2017: 21 · 2016: 2
FWCI
23.17
Type
journal article
Language
en
Open access
Locations
  • Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
Funders
  • National Institutes of Health (4ul1tr000448-10)
  • National Center for Advancing Translational Sciences (UL1-TR-000448)
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, misdiagnosis, demyelinating disease, migraine, fibromyalgia, conversion disorder, psychogenic disorders, neuromyelitis optica spectrum disorder, MRI abnormalities, diagnostic criteria, disease-modifying therapy, atypical presentation
MeSH terms
Academic Medical Centers, Clinical Trials as Topic, Diagnostic Errors, Female, Humans, Male, Middle Aged, Multiple Sclerosis, United States, Biomarkers, Immunomodulation

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