Skip to main content

Advertisement

Log in

Misdiagnosis of Multiple Sclerosis: Frequency, Causes, Effects, and Prevention

  • Demyelinating Disorders (DN Bourdette and V Yadav, Section Editors)
  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

A diagnosis of multiple sclerosis is heavily influenced by clinical judgment. Misdiagnosis of multiple sclerosis is common and has important consequences for patients and the cost of healthcare. Although rigorous data about the frequency and causes of misdiagnosis are lacking, misinterpretation and misapplication of clinical and radiographic diagnostic criteria and terminology are likely important factors. Appropriate and stringent application of diagnostic criteria and continued vigilance for “red flags” suggesting alternative diagnoses are strategies critical for prevention of misdiagnosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Millar JH, Allison RS. Familial incidence of disseminated sclerosis in Northern Ireland. Ulster Med J. 1954;23 Suppl 2:29–92.

    PubMed  CAS  Google Scholar 

  2. Poser CM, Brinar VV. Diagnostic criteria for multiple sclerosis: an historical review. Clin Neurol Neurosurg. 2004;106:147–58. doi:10.1016/j.clineuro.2004.02.004.

    Article  PubMed  Google Scholar 

  3. Broman T, Bergmann L, Fog T, Gilland O, Hyllested K, Lindberg-Broman AM, et al. Aspects on classification methods in multiple sclerosis. Acta Neurol Scand Suppl. 1965;13(Pt 2):543–8.

    PubMed  Google Scholar 

  4. Schumacker GA, Beebe G, Kibler RF, Kurland LT, Kurtzke JF, McDowell F, et al. Problems of Experimental Trials of Therapy in Multiple Sclerosis: report by the Panel on The Evaluation of Experimental Trials of Therapy in Multiple Sclerosis. Ann NY Acad Sci. 1965;122:552–68.

    Article  PubMed  CAS  Google Scholar 

  5. Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, Ebers GC, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. 1983;13:227–31. doi:10.1002/ana.410130302.

    Article  PubMed  CAS  Google Scholar 

  6. McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50:121–7.

    Article  PubMed  CAS  Google Scholar 

  7. Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005;58:840–6. doi:10.1002/ana.20703.

    Article  PubMed  Google Scholar 

  8. Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69:292–302. doi:10.1002/ana.22366.

    Article  PubMed  Google Scholar 

  9. •• Selchen D, Bhan V, Blevins G, Devonshire V, Duquette P, Grand'Maison F, et al. MS, MRI, and the 2010 McDonald criteria: a Canadian expert commentary. Neurology. 2012;79(23 Suppl 2):S1–S15. doi:10.1212/WNL.0b013e318277d144. Important contemporary commentary regarding the limitations of current MS diagnostic crtieria.

    Article  PubMed  Google Scholar 

  10. Herndon RM. Multiple sclerosis mimics. Adv Neurol. 2006;98:161–6.

    PubMed  Google Scholar 

  11. Bowen J. Diagnosing multiple sclerosis and its imitators. Phys Med Rehab Clin NA. 2005;16:359–81. doi:10.1016/j.pmr.2005.01.011.

    Article  Google Scholar 

  12. Miller DH, Weinshenker BG, Filippi M, Banwell BL, Cohen JA, Freedman MS, et al. Differential diagnosis of suspected multiple sclerosis: a consensus approach. Mult Scler. 2008;14:1157–74. doi:10.1177/1352458508096878.

    Article  PubMed  CAS  Google Scholar 

  13. Natowicz MR, Bejjani B. Genetic disorders that masquerade as multiple sclerosis. Am J Med Genet. 1994;49:149–69. doi:10.1002/ajmg.1320490202.

    Article  PubMed  CAS  Google Scholar 

  14. Davis RL, Robertson DM. Textbook of neuropathology. 2nd ed. Baltimore: Williams & Wilkins; 1990.

    Google Scholar 

  15. Engell T. A clinico-pathoanatomical study of multiple sclerosis diagnosis. Acta Neurol Scand. 1988;78:39–44.

    Article  PubMed  CAS  Google Scholar 

  16. Herndon RMBB. Misdiagnosis of multiple sclerosis. Semin Neurol. 1985;5:94–8.

    Article  Google Scholar 

  17. Rudick RA, Schiffer RB, Schwetz KM, Herndon RM. Multiple sclerosis. The problem of incorrect diagnosis. Arch Neurol. 1986;43:578–83.

    Article  PubMed  CAS  Google Scholar 

  18. Noseworthy JH, Rice GP. Trichlorethylene poisoning mimicking multiple sclerosis. Can J Neurol Sci. 1988;15:87–8.

    PubMed  CAS  Google Scholar 

  19. Bender GP, Schapiro RT. Primary CNS lymphoma presenting as multiple sclerosis. A case study. Minn Med. 1989;72:157–60.

    PubMed  CAS  Google Scholar 

  20. Bussone G, La Mantia L, Grazzi L, Lamperti E, Salmaggi A, Strada L. Neurobrucellosis mimicking multiple sclerosis: a case report. Eur Neurol. 1989;29:238–40.

    Article  PubMed  CAS  Google Scholar 

  21. Scott TF, Hess D, Brillman J. Antiphospholipid antibody syndrome mimicking multiple sclerosis clinically and by magnetic resonance imaging. Arch Int Med. 1994;154:917–20.

    Article  CAS  Google Scholar 

  22. Vrethem M, Thuomas KA, Hillman J. Cavernous angioma of the brain stem mimicking multiple sclerosis. N Engl J Med. 1997;336:875–6. doi:10.1056/nejm199703203361213.

    Article  PubMed  CAS  Google Scholar 

  23. Dougan CF, Coulthard A, Cartlidge NE, Burn DJ. Familial cavernous angiomas masquerading as multiple sclerosis. Postgrad Med J. 1998;74:489–91.

    Article  PubMed  CAS  Google Scholar 

  24. Russo MB, Brooks FR, Fontenot J, Dopler BM, Neely ET, Halliday AW. Conversion disorder presenting as multiple sclerosis. Milit Med. 1998;163:709–10.

    CAS  Google Scholar 

  25. Cader MZ, Winer JB. Lesson of the week: cavernous haemangioma mimicking multiple sclerosis. BMJ (Clin Res ed). 1999;318:1604–5.

    Article  CAS  Google Scholar 

  26. Ormsby A, Prayson RA, Heard R. Angiotrophic large cell lymphoma mimicking multiple sclerosis associated transverse myelitis. J Clin Neurosci. 1999;6:408–10. doi:10.1054/jocn.1998.0091.

    Article  PubMed  Google Scholar 

  27. Evans RW, Rolak LA. Migraine vs multiple sclerosis. Headache. 2001;41:97–8.

    Article  PubMed  CAS  Google Scholar 

  28. O'Riordan S, Nor AM, Hutchinson M. CADASIL imitating multiple sclerosis: the importance of MRI markers. Mult Scler. 2002;8:430–2.

    Article  PubMed  Google Scholar 

  29. Tiryaki E, Azzarelli B, Biller J. Superficial siderosis of the central nervous system in a patient with chronic subarachnoid hemorrhage misdiagnosed as multiple sclerosis. J Stroke Cerebrovasc Dis. 2002;11:288–9. doi:10.1053/jscd.2002.129618.

    Article  PubMed  Google Scholar 

  30. Fernandez-Fernandez FJ, Rivera-Gallego A, de la Fuente-Aguado J, Perez-Fernandez S, Munoz-Fernandez D. Antiphospholipid syndrome mimicking multiple sclerosis in two patients. Eur J Int Med. 2006;17:500–2. doi:10.1016/j.ejim.2006.02.018.

    Article  CAS  Google Scholar 

  31. Rafalowska J, Dziewulska D, Podlecka A, Zakrzewska-Pniewska B. Extensive mixed vascular malformation clinically imitating multiple sclerosis—case report. Clin Neuropathol. 2006;25:237–42.

    PubMed  CAS  Google Scholar 

  32. Saip S, Uluduz D, Erkol G. Fabry disease mimicking multiple sclerosis. Clin Neurol Neurosurg. 2007;109:361–3. doi:10.1016/j.clineuro.2006.12.006.

    Article  PubMed  Google Scholar 

  33. Beeravolu LR, Frohman EM, Frohman TC, Remington GM, Lee S, Levin MC. Pearls & Oy-sters: "Not multiple sclerosis" and the changing face of HTLV-1: a case report of downbeat nystagmus. Neurology. 2009;72:e119–20. doi:10.1212/WNL.0b013e3181aa5316.

    Article  PubMed  CAS  Google Scholar 

  34. Boentert M, Kraus J, Kloska S, Dittrich R, Nabavi DG, Niederstadt T, et al. Obliterating intracranial vasculopathy mimicking multiple sclerosis. Acta Neurol Scand. 2009;120:68–71. doi:10.1111/j.1600-0404.2008.01121.x.

    Article  PubMed  CAS  Google Scholar 

  35. Chebel S, Barboura I, Boughammoura-Bouatay A, Ammar M, Ferchichi S, Miled A, et al. Adult-type metachromatic leukodystrophy mimicking multiple sclerosis. Can J Neurol Sci. 2009;36:521–3.

    PubMed  Google Scholar 

  36. Matsuo Y, Kamezaki K, Takeishi S, Takenaka K, Eto T, Nonami A, et al. Encephalomyelitis mimicking multiple sclerosis associated with chronic graft-vs-host disease after allogeneic bone marrow transplantation. Int Med (Tokyo, Japan). 2009;48:1453–6.

    Article  Google Scholar 

  37. Papadimas GK, Rentzos M, Zouvelou V, Kilidireas K, Konstantinopoulou A, Kokotis P, et al. Superficial siderosis of central nervous system mimicking multiple sclerosis. Neurologist. 2009;15:153–5. doi:10.1097/NRL.0b013e31818a5d3a.

    Article  PubMed  CAS  Google Scholar 

  38. Brinar VV, Habek M. Rare infections mimicking MS. Clin Neurol Neurosurg. 2010;112:625–8. doi:10.1016/j.clineuro.2010.04.011.

    Article  PubMed  Google Scholar 

  39. Utsuki S, Oka H, Miyazaki T, Yamazaki T, Yasui Y, Fujii K, et al. Primary central nervous system large B-cell lymphoma with prolific, mixed T-cell and macrophage infiltrates, mimicking multiple sclerosis. Brain Tumor Pathol. 2010;27:59–63. doi:10.1007/s10014-010-0264-x.

    Article  PubMed  Google Scholar 

  40. Stricker RB, Johnson L. 'Rare' infections mimicking multiple sclerosis: consider Lyme disease. Clin Neurol Neurosurg. 2011;113:259–60. doi:10.1016/j.clineuro.2010.11.017.

    Article  PubMed  Google Scholar 

  41. Dorfman LJ, Fischbein NJ, Woodard JI, Choudhri O, Bell-Stephens TE, Steinberg GK. Moyamoya disease can masquerade as multiple sclerosis. Neurologist. 2012;18:398–403. doi:10.1097/NRL.0b013e31826a99a1.

    Article  PubMed  Google Scholar 

  42. Ohe Y, Hayashi T, Mishima K, Nishikawa R, Sasaki A, Matsuda H, et al. Central nervous system lymphoma initially diagnosed as tumefactive multiple sclerosis after brain biopsy. Int Med (Tokyo, Japan). 2013;52:483–8.

    Article  Google Scholar 

  43. Murray TJ, Murray SJ. Characteristics of patients found not to have multiple sclerosis. Can Med Assoc J. 1984;131:336–7.

    PubMed  CAS  Google Scholar 

  44. Carmosino MJ, Brousseau KM, Arciniegas DB, Corboy JR. Initial evaluations for multiple sclerosis in a university multiple sclerosis center: outcomes and role of magnetic resonance imaging in referral. Arch Neurol. 2005;62:585–90. doi:10.1001/archneur.62.4.585.

    Article  PubMed  Google Scholar 

  45. Brousseau KM, Arciniegas DB, Carmosino MJ, Corboy JR. The differential diagnosis of Axis I psychopathology presenting to a university-based multiple sclerosis clinic. Mult Scler. 2007;13:749–53. doi:10.1177/1352458506075032.

    Article  PubMed  CAS  Google Scholar 

  46. Pelidou SH, Giannopoulos S, Tzavidi S, Tsifetaki N, Kitsos G, Stefanou D, et al. Neurological manifestations of connective tissue diseases mimicking multiple sclerosis. Rheumatol Int. 2007;28:15–20. doi:10.1007/s00296-007-0384-8.

    Article  PubMed  Google Scholar 

  47. Poser CM. Misdiagnosis of multiple sclerosis and beta-interferon. Lancet. 1997;349:1916. doi:10.1016/s0140-6736(05)63920-7.

    Article  PubMed  CAS  Google Scholar 

  48. Nielsen JM, Korteweg T, Barkhof F, Uitdehaag BM, Polman CH. Overdiagnosis of multiple sclerosis and magnetic resonance imaging criteria. Ann Neurol. 2005;58:781–3. doi:10.1002/ana.20632.

    Article  PubMed  Google Scholar 

  49. • Solomon AJ, Klein EP, Bourdette D. "Undiagnosing" multiple sclerosis: the challenge of misdiagnosis in MS. Neurology. 2012;78:1986–91. doi:10.1212/WNL.0b013e318259e1b2. Recent survey concerning MS misdiagnosis providing data on frequency and hypothesized causes.

  50. Poser CM, Brinar VV. Problems with diagnostic criteria for multiple sclerosis. Lancet. 2001;358:1746–7. doi:10.1016/s0140-6736(01)06842-8.

    Google Scholar 

  51. Rudick RA. Diagnostic criteria in multiple sclerosis: headed in the right direction but still a ways to go. Ann Neurol. 2011;69:234–6. doi:10.1002/ana.22388.

    Article  PubMed  Google Scholar 

  52. Schiffer RB, Giang DW, Mushlin A, Ketonen L, Joy S, Kido D, et al. Perils and pitfalls of magnetic resonance imaging in the diagnosis of multiple sclerosis. The Rochester-Toronto MRI Study Group. J Neuroimag. 1993;3:81–8.

    CAS  Google Scholar 

  53. Whiting P, Harbord R, Main C, Deeks JJ, Filippini G, Egger M, et al. Accuracy of magnetic resonance imaging for the diagnosis of multiple sclerosis: systematic review. BMJ (Clin Res Ed). 2006;332:875–84. doi:10.1136/bmj.38771.583796.7C.

    Article  Google Scholar 

  54. Kim SS, Richman DP, Johnson WO, Hald JK, Agius MA. Limited utility of current MRI criteria for distinguishing multiple sclerosis from common mimickers: primary and secondary CNS vasculitis, lupus and Sjogren's syndrome. Multiple Sclerosis. 2013. doi:10.1177/1352458513491329.

  55. • Liu S, Kullnat J, Bourdette D, Simon J, Kraemer DF, Murchison C, et al. Prevalence of brain magnetic resonance imaging meeting Barkhof and McDonald criteria for dissemination in space among headache patients. Multiple Sclerosis. 2013. doi:10.1177/1352458512471874. Recent study demonstrating the limitations of MS imaging crtieria.

  56. Charil A, Yousry TA, Rovaris M, Barkhof F, De Stefano N, Fazekas F, et al. MRI and the diagnosis of multiple sclerosis: expanding the concept of "no better explanation". Lancet Neurol. 2006;5:841–52. doi:10.1016/s1474-4422(06)70572-5.

    Article  PubMed  Google Scholar 

  57. Polman CH, Wolinsky JS, Reingold SC. Multiple sclerosis diagnostic criteria: three years later. Mult Scler. 2005;11:5–12.

    Article  PubMed  Google Scholar 

  58. Okuda DT, Mowry EM, Beheshtian A, Waubant E, Baranzini SE, Goodin DS, et al. Incidental MRI anomalies suggestive of multiple sclerosis: the radiologically isolated syndrome. Neurology. 2009;72:800–5. doi:10.1212/01.wnl.0000335764.14513.1a.

    Article  PubMed  CAS  Google Scholar 

  59. Bourdette D, Yadav V. The radiologically isolated syndrome revisited: when is it presymptomatic multiple sclerosis? Neurology. 2011;76:680–1. doi:10.1212/WNL.0b013e31820e7769.

    Article  PubMed  Google Scholar 

  60. Bourdette D, Yadav V. Treat patients with radiologically isolated syndrome when the MRI brain scan shows dissemination in time no. Multiple. 2012;18:1529–30. doi:10.1177/1352458512462075.

    Article  Google Scholar 

  61. Spain R, Bourdette D. The radiologically isolated syndrome: look (again) before you treat. Curr Neurol Neurosci Rep. 2011;11:498–506. doi:10.1007/s11910-011-0213-z.

    Article  PubMed  Google Scholar 

  62. Groopman JE. How doctors think. Boston: Houghton Mifflin; 2007.

    Google Scholar 

  63. Boissy AR, Ford PJ. A touch of MS: therapeutic mislabeling. Neurology. 2012;78:1981–5. doi:10.1212/WNL.0b013e318259e0ec.

    Article  PubMed  Google Scholar 

  64. Tullman MJ. Overview of the epidemiology, diagnosis, and disease progression associated with multiple sclerosis. Am J Manag Care. 2013;19(2 Suppl):S15–20.

    PubMed  Google Scholar 

  65. Rudick RA, Miller AE. Multiple sclerosis or multiple possibilities: the continuing problem of misdiagnosis. Neurology. 2012;78:1904–6. doi:10.1212/WNL.0b013e318259e2e2.

    Article  PubMed  Google Scholar 

  66. Solomon AJ, Klein E. Disclosing a misdiagnosis of multiple sclerosis: do no harm? Continuum. 2013;19(4 Multiple Sclerosis):1087–91. doi:10.1212/01.CON.0000433281.18146.5b.

    PubMed  Google Scholar 

  67. Kohn LT, Corrigan J, Donaldson MS. To err is human: building a safer health system. Washington: National Academy Press; 2000.

    Google Scholar 

  68. Dobson R, Ramagopalan S, Davis A, Giovannoni G. Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: a meta-analysis of prevalence, prognosis and effect of latitude. J Neurol Neurosurg Psychiatry. 2013. doi:10.1136/jnnp-2012-304695.

  69. Alvarez-Cermeno JC, Villar LM. Multiple sclerosis: oligoclonal bands-a useful tool to avoid MS misdiagnosis. Nature Rev Neurol. 2013. doi:10.1038/nrneurol.2013.74.

  70. Hutchinson M. CSF oligoclonal bands are important in the diagnosis of multiple sclerosis, unreasonably downplayed by the McDonald Criteria 2010: commentary. Mult Scler. 2013;19:719–20. doi:10.1177/1352458513485496.

    Article  PubMed  Google Scholar 

  71. Sandberg-Wollheim M, Olsson T. Cerebrospinal fluid oligoclonal bands are important in the diagnosis of multiple sclerosis, unreasonably downplayed by the McDonald criteria 2010: yes. Mult Scler. 2013;19:714–6. doi:10.1177/1352458513480011.

    Article  PubMed  Google Scholar 

  72. Bates D. Treatment effects of immunomodulatory therapies at different stages of multiple sclerosis in short-term trials. Neurology. 2011;76(1 Suppl 1):S14–25. doi:10.1212/WNL.0b013e3182050388.

    Article  PubMed  CAS  Google Scholar 

  73. Coyle PK. Early treatment of multiple sclerosis to prevent neurologic damage. Neurology. 2008;71(24 Suppl 3):S3–7. doi:10.1212/WNL.0b013e31818f3d6f.

    Article  PubMed  CAS  Google Scholar 

  74. Goodin DS, Reder AT, Ebers GC, Cutter G, Kremenchutzky M, Oger J, et al. Survival in MS: a randomized cohort study 21 years after the start of the pivotal IFNbeta-1b trial. Neurology. 2012;78:1315–22. doi:10.1212/WNL.0b013e3182535cf6.

    Article  PubMed  CAS  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Andrew J. Solomon declares that he has no conflict of interest. Brian G. Weinshenker has been a consultant for GSK Pharmaceuticals, Chord Pharmaceuticals, Ono Pharmaceuticals, Guthy Jackson Charitable Foundation; he has received grant support from Guthy Jackson Charitable Foundation; he has received patents (planned, pending, or issued) for AQP4 antibodies for diagnosis of NMO; and he has received royalties from RSR Ltd. for AQP4 antibodies for diagnosis of NMO.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Andrew J. Solomon.

Additional information

This article is part of the Topical Collection on Demyelinating Disorders

Rights and permissions

Reprints and permissions

About this article

Cite this article

Solomon, A.J., Weinshenker, B.G. Misdiagnosis of Multiple Sclerosis: Frequency, Causes, Effects, and Prevention. Curr Neurol Neurosci Rep 13, 403 (2013). https://doi.org/10.1007/s11910-013-0403-y

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11910-013-0403-y

Keywords

Navigation