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September 27, 2016; 87 (13) Contemporary Issues

The contemporary spectrum of multiple sclerosis misdiagnosis

A multicenter study

Andrew J. Solomon, Dennis N. Bourdette, Anne H. Cross, Angela Applebee, Philip M. Skidd, Diantha B. Howard, Rebecca I. Spain, Michelle H. Cameron, Edward Kim, Michele K. Mass, Vijayshree Yadav, Ruth H. Whitham, Erin E. Longbrake, Robert T. Naismith, Gregory F. Wu, Becky J. Parks, Dean M. Wingerchuk, Brian L. Rabin, Michel Toledano, W. Oliver Tobin, Orhun H. Kantarci, Jonathan L. Carter, B. Mark Keegan, Brian G. Weinshenker
First published August 31, 2016, DOI: https://doi.org/10.1212/WNL.0000000000003152
Andrew J. Solomon
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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Dennis N. Bourdette
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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Anne H. Cross
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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Angela Applebee
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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Philip M. Skidd
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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Diantha B. Howard
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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Rebecca I. Spain
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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Michelle H. Cameron
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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Edward Kim
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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Michele K. Mass
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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Vijayshree Yadav
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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Ruth H. Whitham
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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Erin E. Longbrake
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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Robert T. Naismith
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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Gregory F. Wu
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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Becky J. Parks
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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Dean M. Wingerchuk
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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Brian L. Rabin
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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Michel Toledano
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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W. Oliver Tobin
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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Orhun H. Kantarci
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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Jonathan L. Carter
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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B. Mark Keegan
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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Brian G. Weinshenker
From the Departments of Neurological Sciences (A.J.S., A.A.) and Ophthalmology (P.M.S.), and Center for Clinical and Translational Science (D.B.H.), University of Vermont, Burlington; Department of Neurology (D.N.B., R.I.S., M.H.C., E.K., M.K.M., V.Y., R.H.W.), Oregon Health & Science University, Portland; Department of Neurology (A.H.C., E.E.L., R.T.N., G.F.W., B.J.P.), Washington University, St. Louis, MO; Department of Neurology (D.M.W., B.L.R., J.L.C.), Mayo Clinic, Scottsdale, AZ; and Department of Neurology (M.T., W.O.T., O.H.K., B.M.K., B.G.W.), Mayo Clinic, Rochester, MN.
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Full PDF
Citation
The contemporary spectrum of multiple sclerosis misdiagnosis
A multicenter study
Andrew J. Solomon, Dennis N. Bourdette, Anne H. Cross, Angela Applebee, Philip M. Skidd, Diantha B. Howard, Rebecca I. Spain, Michelle H. Cameron, Edward Kim, Michele K. Mass, Vijayshree Yadav, Ruth H. Whitham, Erin E. Longbrake, Robert T. Naismith, Gregory F. Wu, Becky J. Parks, Dean M. Wingerchuk, Brian L. Rabin, Michel Toledano, W. Oliver Tobin, Orhun H. Kantarci, Jonathan L. Carter, B. Mark Keegan, Brian G. Weinshenker
Neurology Sep 2016, 87 (13) 1393-1399; DOI: 10.1212/WNL.0000000000003152

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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.

GLOSSARY

IgG=
immunoglobulin G;
MS=
multiple sclerosis;
NMOSD=
neuromyelitis optica spectrum disorder;
OCB=
oligoclonal band

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received January 28, 2016.
  • Accepted in final form June 9, 2016.
  • © 2016 American Academy of Neurology
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    • Andrew J. Solomon, University of Vermontandrew.solomon@uvm.edu
    • Brian G. Weinshenker
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