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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

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Miller, DH, Weinshenker, BG, Filippi, M, Banwell, BL, Cohen, JA, Freedman, MS, Galetta, SL, Hutchinson, M +10 more·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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Research works printed but not linked: 61

  1. [1]Schumacher FA Beeve GW Kibler FR Problems of experimental trials of therapy in multiple sclerosis. Ann NY Acad Sci 1965; 122: 552– 568 14313512
  2. [2]Poser CM Paty DW Scheinberg LC New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983; 13: 227– 231 6847134
  3. [3]McDonald WI Compston A Edan G Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 2001; 50: 121– 127 11456302
  4. [4]Polman CH Reingold SC Edan G Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol 2005; 58: 840– 846 16283615
  5. [5]Charil A Yousry TA Rovaris M MRI and the diagnosis of multiple sclerosis: expanding the concept of “no better explanation”. Lancet Neurol 2006; 5: 841– 852 16987731
  6. [6]Jacobs LD Beck RW Simon JH Intramuscular interferon beta-1a therapy initiated during a first demye-linating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med 2000; 343: 898– 904 11006365
  7. [7]Comi G Filippi M Barkhof F Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomized study. Lancet 2001; 357: 1576– 1582 11377645
  8. [8]Kappos L Polman CH Freedman MS Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology 2006; 10: 1242– 1249 16914693
  9. [9]Swanton JK Rovira A Tintoré M MRI criteria for multiple sclerosis in patients presenting with clinically isolated syndromes: a multicentre retrospective study. Lancet Neurol 2007; 6: 677– 686 17616439
  10. [10]Ormerod IE Miller DH McDonald WI The role of NMR imaging in the assessment of multiple sclerosis and isolated neurological lesions. A quantitative study. Brain 1987; 110: 1579– 1616 3427402
  11. [11]Uitdehaag BMJ Kappos L Bauer L Discrepancies in the interpretation of clinical symptoms and signs in the diagnosis of MS: a proposal for standardization. Mult Scler 2005; 11: 227– 231 15794398
  12. [12]Mastronardo G Rocca MA Iannucci G Pereira C Filippi M A longitudinal MR study of the presymptomatic phase in a patient with clinically definite multiple sclerosis. Am J Neuroradiol 1999; 20: 1268– 1272 10472984 PMC7055993
  13. [14]Minneboo A Barkhof F Polman CH Uitdehaag BM Knol DL Castelijns JA Infratentorial lesions predict long-term disability in patients with initial findings suggestive of multiple sclerosis. Arch Neurol 2004; 61: 217– 221 14967769
  14. [15]Optic Neuritis Study Group. Long-term brain magnetic resonance imaging changes after optic neuritis in patients without clinically definite multiple sclerosis. Arch Neurol 2004; 61: 1538– 1541 15477507
  15. [16]Tintoré M Rovira A Rio J Baseline MRI predicts future attacks and disability in clinically isolated syndromes. Neurology 2006; 67: 968– 972 17000962
  16. [17]Kangarlu A Bourekas EC Ray-Chaudhury A Rammohan KW Cerebral cortical lesions in multiple sclerosis detected by MR imaging at 8 Tesla Am J Neuroradiol 2007; 28: 262– 266 17296991 PMC7977406
  17. [18]Lebrun C Bensa C Debouverie M Unexpected multiple sclerosis: follow-up of 30 patients with magnetic resonance imaging and clinical conversion profile J Neurol Neurosurg Psychiatry 2008; 79: 195– 198 18202208
  18. [19]Wingerchuk DM Lennon VA Pittock SJ Lucchinetti CF Weinshenker BG Revised diagnostic criteria for neuromyelitis optica Neurology 2006; 66: 1485– 1489 16717206
  19. [20]Saiz A Zuliani L Blanco Y Revised diagnostic criteria for neuromyelitis optica: application in a series of suspected patients J Neurol 2007; 254: 1233– 1237 17401734
  20. [21]Cohen O Steiner-Birmanns B Biran I Abramsky O Honigman S Steiner I Recurrence of acute disseminated encephalomyelitis at the previously affected brain site Arch Neurol 2001; 58: 797– 701 11346375
  21. [22]Hartung HP Grossman RI ADEM: distinct disease or part of the MS spectrum Neurology 2001; 56: 1257– 1260 11376169
  22. [23]Anlar B Basaran C Kose G Acute disseminated encephalomyelitis in children: outcome and prognosis Neuropediatrics 2003; 24: 194– 199 12973660
  23. [24]Morimatsu M Recurrent ADEM or MS Int Med 2004; 43: 647– 648 15468960
  24. [25]Jacob A Matiello M Wingerchuk DM Lucchinetti CF Pittock SJ Weinshenker BG Neuromyelitis optica: changing concepts J Neuroimmunol 2007; 187: 126– 138 17512987
  25. [26]Wingerchuk DM Lennon VA Lucchinetti CF Pittock SJ Weinshenker BG The spectrum of neuromyelitis optica Lancet Neurol 2007; 6: 805– 815 17706564
  26. [27]O'Riordan JI Gallagher HL Thompson AJ Clinical, CSF and MRI findings in Devic's neuromyelitis optica J Neurol Neurosurg Psychiatry 1996; 60: 382– 387 8774400 PMC1073888
  27. [28]Wingerchuk DM Hogancamp WF O'Brien PC Weinshenker BG The clinical course of neuromyelitis optica (Devic's syndrome) Neurology 1999; 53: 1107– 1114 10496275
  28. [29]de Seze J Neuromyelitis optica Arch Neurol 2003; 60: 1336– 1338 12975307
  29. [30]de Seze J Lebrun C Stojkovic T Ferriby D Chatel M Vermersch P Is Devic's neuromyelitis optica a separate disease? A comparative study with multiple sclerosis Mult Scler 2003; 9: 521– 525 14582780
  30. [31]Ghezzi A Bergamaschi R Martinelli V Clinical characteristics, course and prognosis of relapsing Devic's Neuromyelitis Optica J Neurol 2004; 251: 47– 52 14999489
  31. [32]Lennon VA Wingerchuk DM Kryzer TJ A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004; 364: 2106– 2112 15589308
  32. [33]Jarius S Franciotta D Bergamaschi R NMO-IgG in the diagnosis of neuromyelitis optica. Neurology 2007; 68: 1076– 1077 17287449
  33. [34]Keegan M Pineada AA McClelland RL Darby CH Rodriguez M Weinshenker BG Plasma exchange for severe attacks of CNS demyelination: predictors of response. Neurology 2003; 58: 143– 146 11781423
  34. [35]Papeix C Vidal JS de Seze J Immunosuppressive therapy is more effective than interferon in neuromyelitis optica. Mult Scler 2007; 13: 256– 259 17439893
  35. [36]Warabi Y Matsumoto Y Hayashi H Interferon beta-1b exacerbates multiple sclerosis with severe optic nerve and spinal cord demyelination. J Neurol Sci 2007; 252: 257– 261 17125797
  36. [37]Mandler RN Davis LE Jeffery DR Kornfeld M Devic's neuromyelitis optica: a clinicopathological study of 8 patients. Ann Neurol 1993; 34: 162– 168 8338340
  37. [38]Filippi M Rocca MA Moiola L MRI and magnetization transfer imaging changes in the brain and cervical cord of patients with Devic's neuromyelitis optica. Neurology 1999; 53: 1705– 1710 10563616
  38. [39]Rocca MA Agosta F Mezzapesa DM Magnetization transfer and diffusion tensor MRI show gray matter damage in neuromyelitis optica. Neurology 2004; 10: 476– 478 14872036
  39. [40]Barkhof F Filippi M Miller DH Comparison of MR imaging criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain 1997; 120: 2059– 2069 9397021
  40. [41]Pittock SJ Lennon VA Wingerchuk DM Lucchinetti CF Weinshenker BG Brain abnormalities in neuromyelitis optica. Arch Neurol 2006; 63: 390– 396 16533966
  41. [42]Pittock SJ Weinshenker GB Lucchinetti CF Wingerchuk DM Corboy JR Lennon VA Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression. Arch Neurol 2006; 63: 964– 968 16831965
  42. [43]Bergamaschi R Tonietti S Franciotta D Oligoclonal bands in Devic's neuromyelitis optica and multiple sclerosis. Differences in repeated cerebrospinal fluid examinations. Mult Scler 2004; 10: 2– 4 14760945
  43. [44]Weinshenker BG Wingerchuk DM Vukusic S Neuromyelitis optica IgG predicts relapse after longitudinal extensive transverse myelitis. Ann Neurol 2006; 59: 566– 569 16453327
  44. [45]Matiello M Lennon VA Jacopb A NMO-IgG predicts the outcome of recurrent optic neuritis. Neurology 2008; 70: 2197– 2220 18434643
  45. [46]Pittock SJ Lennon VA de Seze J Neuromyelitis optica and non-organ-specific autoimmunity. Arch Neurol 2008; 65: 78– 83 18195142
  46. [47]Kira J Multiple sclerosis in the Japanese population. Lancet Neurol 2003; 2: 117– 127 12849268
  47. [48]Matsuoka T Matsushita T Kawano Y Heterogeneity of aquaporin-4 autoimmunity and spinal cord lesions in multiple sclerosis in Japanese. Brain 2007; 130: 1206– 1223 17439988
  48. [49]Kesselring J Miller DH Robb SA Acute disseminated encephalomyelitis. MRI findings and the distinction from multiple sclerosis. Brain 1990; 113: 291– 302 2328406
  49. [50]de Seze J Debouverie M Zephir H Acute fulminant demyelinating disease: a descriptive study of 60 patients. Arch Neurol 2007; 64: 1426– 1432 17923626
  50. [51]Banwell B Shroff M Ness JM MRI features of pediatric multiple sclerosis. Neurology 2007; 68 (Suppl. 2): S46– S53 17438238
  51. [52]Krupp LB Banwell B Tenembaum S for the International Pediatric MS Study Group. Consensus definitions proposed for pediatric multiple sclerosis and related disorders. Neurology 2007; 68 (Suppl. 2): S7– S12 17438241
  52. [53]Brinar VV Poser CM The spectrum of disseminated encephalomyelitis. Clin Neurol Neurosurg 2006; 108: 2295– 2310 16387421
  53. [54]Lublin FD Reingold SC Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 1996; 40: 469– 479 8780061
  54. [55]Mendez MF Pogacar S Malignant monophasic multiple sclerosis or “Marburg's disease”. Neurology 1988; 38: 1153– 1155 3386836
  55. [56]Johnson MD Lavin P Whetsell WO Fuminant monophasic multiple sclerosis, Marburg's type. J Neurol Neurosurg Psychiatry 1990; 53: 918– 921 2266377 PMC488259
  56. [57]Moore GR Neumann PE Suzuki K Lijtmaer HN Traugott U Raine CS Balo's concentric sclerosis: new observations on lesion development. Ann Neurol 1985; 17: 604– 611 4026231
  57. [58]Hunter SB Ballinger WE Jr. Rubin JJ Multiple sclerosis mimicking primary brain tumor. Arch Pathol Lab Med 1987; 111: 464– 468 3566474
  58. [59]Kepes J Large focal tumor-like demyelinating lesions of the brain: intermediate entity between multiple sclerosis and acute disseminated encephalomyelitis: a study of 31 patients. Ann Neurol 1993; 22: 18– 27 8494332
  59. [60]Morrissey SP Miller DH Kendall BE The significance of brain magnetic resonance imaging abnormalities at presentation with clinically isolated syndromes suggestive of multiple sclerosis. A 5-year follow-up study. Brain 1993; 116: 135– 146 8453454
  60. [61]Söderström M Ya-Ping J Hillert J Link H Optic neuritis. Prognosis for multiple sclerosis from MRI, CSF and HLA findings. Neurology 1998; 50: 708– 714 9521261
  61. [62]Weinshenker BG Gilbert JJ Ebers GC Some clinical and pathologic observations on chronic myelopathy: a variant of multiple sclerosis. J Neurol Neurosurg Psychiatry 1990; 53: 146– 149 2313302 PMC487956

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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 › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Family Practice › Clinical Reasoning and Diagnostic Skills
  • Health Sciences › Medicine › 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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